Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCγ2 signaling axis in mice

Graham, Daniel B.; Robertson, Charles M.; Bautista, Jhoanne; Mascarenhas, Francesca; Diacovo, M. Julia; Montgrain, Vivianne; Lam, Siu Kit; Cremasco, Viviana; Dunne, W. Michael; Faccio, Roberta; Coopersmith, Craig M.; Swat, Wojciech

doi:10.1172/jci32729

Cited by 124Neutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stressImmunodeficiency and Autoimmune Disorders

Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCγ2 signaling axis in mice

Open access

Graham, Daniel B., Robertson, Charles M., Bautista, Jhoanne, Mascarenhas, Francesca, Diacovo, M. Julia, Montgrain, Vivianne, Lam, Siu Kit, Cremasco, Viviana +4 more·2007·Journal of Clinical Investigation

DOI 10.1172/jci32729PMC PMC2000813

Open this paper in CoChat — free account

Abstract

Oxidative burst, a critical antimicrobial mechanism of neutrophils, involves the rapid generation and release of reactive oxygen intermediates (ROIs) by the NADPH oxidase complex. Genetic mutations in an NADPH oxidase subunit, gp91 (also referred to as NOX2), are associated with chronic granulomatous disease (CGD), which is characterized by recurrent and life-threatening microbial infections. To combat such infections, ROIs are produced by neutrophils after stimulation by integrin-dependent adhesion to the ECM in conjunction with stimulation from inflammatory mediators, or microbial components containing pathogen-associated molecular patterns. In this report, we provide genetic evidence that both the Vav family of Rho GTPase guanine nucleotide exchange factors (GEFs) and phospholipase C-gamma2 (PLC-gamma2) are critical mediators of adhesion-dependent ROI production by neutrophils in mice. We also demonstrated that Vav was critically required for neutrophil-dependent host defense against systemic infection by Staphylococcus aureus and Pseudomonas aeruginosa, 2 common pathogens associated with fatal cases of hospital-acquired pneumonia. We identified a molecular pathway in which Vav GEFs linked integrin-mediated signaling with PLC-gamma2 activation, release of intracellular Ca2+ cations, and generation of diacylglycerol to control assembly of the NADPH oxidase complex and ROI production by neutrophils. Taken together, our data indicate that integrin-dependent signals generated during neutrophil adhesion contribute to the activation of NADPH oxidase by a variety of distinct effector pathways, all of which require Vav.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1172/jci32729

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

PLCγ2 is critical for neutrophil-dependent host defense against bacterial infections in vivo.
“In addition to FcR signaling requiring PLCγ2 for efficient ROS production in murine neutrophils, PLCγ2 is also essential for postintegrin signaling induction of ROS, as well as being critical for the neutrophil-dependent host defense against bacterial infections in vivo (80).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [80]
The Figure 3/Figure 6 passages show that PLC-γ2-deficient neutrophils fail to produce reactive oxygen intermediates after adhesion-dependent stimulation. The in vivo bacterial-infection experiments described with Figure 2 tested Vav-deficient mice, not PLC-γ2-deficient mice, so the paper does not directly establish that PLC-γ2 is critical for host defense in vivo. (LLM, conf=0.88)
Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia
(2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200405-644st · Cited by 5,870 · see citing works
NOX enzymes and the biology of reactive oxygen
Lambeth, J. D. (2004) · Nature Reviews Immunology · doi:10.1038/nri1312 · Cited by 3,125 · see citing works
Neutrophils and immunity: challenges and opportunities
Nathan, C. (2006) · Nature reviews. Immunology · doi:10.1038/nri1785 · Cited by 2,971 · see citing works
National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2003, issued August 2003
System, A. R. F. T. N. (2003) · American Journal of Infection Control · doi:10.1016/j.ajic.2003.09.002 · Cited by 2,923 · see citing works
Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1
Abo, A., Pick, E., Hall, A., Totty, N. F., Teahan, C. G., & Segal, A. W. (1991) · Nature · doi:10.1038/353668a0 · Cited by 954 · see citing works
Mouse model of x-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production
Pollock, J. D., Williams, D. A., Gifford, M. A. C., Li, L. L., Du, X., Fisherman, J., Orkin, S. H., Doerschuk, C. M., & Dinauer, M. C. (1995) · Nature Genetics · doi:10.1038/ng0295-202 · Cited by 921 · see citing works
National Nosocomial Infections Surveillance (NNIS) System Report, Data Summary from January 1990-May 1999, Issued June 1999
(1999) · American Journal of Infection Control · doi:10.1016/s0196-6553(99)70031-3 · Cited by 899 · see citing works
Regulation of Phagocyte Oxygen Radical Production by the GTP-Binding Protein Rac 2
Knaus, U. G., Heyworth, P. G., Evans, T., Curnutte, J. T., & Bokoch, G. (1991) · Science · doi:10.1126/science.1660188 · Cited by 673 · see citing works
The PX domains of p47phox and p40phox bind to lipid products of PI(3)K
Kanai, F., Liu, H., Field, S. J., Akbary, H., Matsuo, T., Brown, G. E., Cantley, L. C., & Yaffe, M. B. (2001) · Nature Cell Biology · doi:10.1038/35083070 · Cited by 611 · see citing works
Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins.
Nathan, C., Srimal, S., Farber, C., Sánchez, E., Kabbash, L. G., Asch, A., Gailit, J. O., & Wright, S. D. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.109.3.1341 · Cited by 556 · see citing works
Deficiency of the Hematopoietic Cell-Specific Rho Family GTPase Rac2 Is Characterized by Abnormalities in Neutrophil Function and Host Defense
Roberts, A. W., Kim, C., Zhen, L., Lowe, J. B., Kapur, R., Petryniak, B., Spaetti, A., Pollock, J. D., Borneo, J. B., Bradford, G. B., et al. (1999) · Immunity · doi:10.1016/s1074-7613(00)80019-9 · Cited by 556 · see citing works
Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation
Ambruso, D. R., Knall, C., Abell, A. N., Panepinto, J. A., Kurkchubasche, A. G., Thurman, G. W., Gonzalez-Aller, C., Hiester, A. A., deBoer, M., Harbeck, R. J., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.080074897 · Cited by 480 · see citing works
Phospholipase Cγ2 Is Essential in the Functions of B Cell and Several Fc Receptors
Wang, D., Feng, J., Wen, R., Marine, J.-C., Sangster, M. Y., Parganas, E., Hoffmeyer, A., Jackson, C. W., Cleveland, J. L., Murray, P. J., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00005-4 · Cited by 475 · see citing works
Syk is required for integrin signaling in neutrophils
Mócsai, A., Zhou, M., Meng, F., Tybulewicz, V. L., & Lowell, C. A. (2002) · Immunity · doi:10.1016/s1074-7613(02)00303-5 · Cited by 421 · see citing works
Infection Control in the ICU
Eggimann, P., & Pittet, D. (2001) · CHEST Journal · doi:10.1378/chest.120.6.2059 · Cited by 396 · see citing works
NADPH oxidases: not just for leukocytes anymore!
Bokoch, G., & Knaus, U. G. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00194-4 · Cited by 383 · see citing works
Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs
Mócsai, A., Abram, C. L., Jakus, Z., Hu, Y., Lanier, L. L., & Lowell, C. A. (2006) · Nature Immunology · doi:10.1038/ni1407 · Cited by 369 · see citing works
Deficiency of Src family kinases p59/61hck and p58c-fgr results in defective adhesion-dependent neutrophil functions.
Lowell, C. A., Fumagalli, L., & Berton, G. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.133.4.895 · Cited by 360 · see citing works
Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency.
Williams, D., Tao, W., Yang, F., Kim, C., Gu, Y., Mansfield, P. J., Levine, J. E., Petryniak, B., Derrow, C. W., Harris, C., et al. (2000) · PubMed · Cited by 334 · see citing works
Molecular composition and regulation of the Nox family NAD(P)H oxidases.
Sumimoto, H., Miyano, K., & Takeya, R. (2005) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2005.08.210 · Cited by 314 · see citing works
Regulation of innate immunity by Rho GTPases
Bokoch, G. (2005) · Trends in Cell Biology · doi:10.1016/j.tcb.2005.01.002 · Cited by 295 · see citing works
SLP76 and SLP65: complex regulation of signalling in lymphocytes and beyond
Koretzky, G. A., Abtahian, F., & Silverman, M. A. (2006) · Nature reviews. Immunology · doi:10.1038/nri1750 · Cited by 278 · see citing works
Respiratory burst in adherent human neutrophils: triggering by colony- stimulating factors CSF-GM and CSF-G
Nathan, C. F. (1989) · Blood · doi:10.1182/blood.v73.1.301.bloodjournal731301 · Cited by 266 · see citing works
Vav1/2/3-null Mice Define an Essential Role for Vav Family Proteins in Lymphocyte Development and Activation but a Differential Requirement in MAPK Signaling in T and B Cells
Fujikawa, K., Miletic, A. V., Alt, F. W., Faccio, R., Brown, T., Hoog, J., Fredericks, J., Nishi, S., Mildiner, S., Moores, S. L., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030874 · Cited by 228 · see citing works
Self-citation
Adhesion-Dependent Degranulation of Neutrophils Requires the Src Family Kinases Fgr and Hck
Mócsai, A., Ligeti, E., Lowell, C. A., & Berton, G. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.2.1120 · Cited by 227 · see citing works
Vav GEFs are required for β2 integrin-dependent functions of neutrophils
Gakidis, M. A. M., Culleré, X., Olson, T. S., Wilsbacher, J. L., Zhang, B., Moores, S. L., Ley, K. F., Swat, W., Mayadas, T. N., & Brugge, J. S. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200404166 · Cited by 222 · see citing works
Self-citation
Vav1 Transduces T Cell Receptor Signals to the Activation of Phospholipase C-γ1 via Phosphoinositide 3-Kinase-dependent and -independent Pathways
Reynolds, L. F., Smyth, L. A., Norton, T., Freshney, N. W., Downward, J., Kioussis, D., & Tybulewicz, V. L. J. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011663 · Cited by 217 · see citing works
Rac2 Is an Essential Regulator of Neutrophil Nicotinamide Adenine Dinucleotide Phosphate Oxidase Activation in Response to Specific Signaling Pathways
Kim, C., & Dinauer, M. C. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.2.1223 · Cited by 207 · see citing works
Long-term follow-up and outcome of 39 patients with chronic granulomatous disease
Liese, J. G., Kloos, S., Jendrossek, V., Petropoulou, T., Wintergerst, U., Notheis, G., Gahr, M. L., & Belohradsky, B. H. (2000) · The Journal of Pediatrics · doi:10.1067/mpd.2000.109112 · Cited by 195 · see citing works
Neutrophils from p40phox−/− mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing
Ellson, C. D., Davidson, K., Ferguson, G., O'Connor, R. P., Stephens, L., & Hawkins, P. T. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052069 · Cited by 182 · see citing works
P-Rex1 Regulates Neutrophil Function
Welch, H. C. E., Condliffe, A. M., Milne, L., Ferguson, G. J., Hill, K., Webb, L. M. C., Okkenhaug, K., Coadwell, W. J., Andrews, S., Thelen, M., et al. (2005) · Current Biology · doi:10.1016/j.cub.2005.09.050 · Cited by 166 · see citing works
Chemoattractant-Stimulated Rac Activation in Wild-Type and Rac2-Deficient Murine Neutrophils: Preferential Activation of Rac2 and Rac2 Gene Dosage Effect on Neutrophil Functions
Li, S., 山内, 明., Marchal, C. C., Molitoris, J. K., Quilliam, L. A., & Dinauer, M. C. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.9.5043 · Cited by 150 · see citing works
P-Rex1 Is a Primary Rac2 Guanine Nucleotide Exchange Factor in Mouse Neutrophils
Dong, X., Mo, Z., Bokoch, G., Guo, C., Li, Z., & Wu, D. (2005) · Current Biology · doi:10.1016/j.cub.2005.09.014 · Cited by 135 · see citing works
Rac2-Deficient Murine Macrophages Have Selective Defects in Superoxide Production and Phagocytosis of Opsonized Particles
山内, 明., Kim, C., Li, S., Marchal, C. C., Towe, J., Atkinson, S. J., & Dinauer, M. C. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.10.5971 · Cited by 133 · see citing works
Impaired Integrin-Dependent Function in Wiskott-Aldrich Syndrome Protein-Deficient Murine and Human Neutrophils
Zhang, H., Schaff, U. Y., Green, C. E., Chen, H., Sarantos, M. R., Hu, Y., Wara, D. W., Simon, S. I., & Lowell, C. A. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.014 · Cited by 131 · see citing works
The Expanding Role for ITAM-Based Signaling Pathways in Immune Cells
Abram, C. L., & Lowell, C. A. (2007) · Science s STKE · doi:10.1126/stke.3772007re2 · Cited by 120 · see citing works
p47 phox Deficiency Impairs NF-κB Activation and Host Defense in Pseudomonas Pneumonia
Sadikot, R. T., Zeng, H., Yull, F. E., Li, B., Cheng, D., Kernodle, D. S., Jansen, D., Contag, C. H., Segal, B. H., Holland, S. M., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.3.1801 · Cited by 108 · see citing works
[Chronic granulomatous disease].
Ck, F., Pasternak, J., & Carvalho Ade, A. (1973) · PubMed · Cited by 107 · see citing works
Role for Plastin in Host Defense Distinguishes Integrin Signaling from Cell Adhesion and Spreading
Chen, H., Mócsai, A., Zhang, H., Ding, R., Morisaki, J. H., White, M. J. V., Rothfork, J. M., Heiser, P. W., Colucci‐Guyon, E., Lowell, C. A., et al. (2003) · Immunity · doi:10.1016/s1074-7613(03)00172-9 · Cited by 101 · see citing works
Chronic Granulomatous Disease; fundamental stages in our understanding of CGD
Assari, T. (2006) · Medical Immunology · doi:10.1186/1476-9433-5-4 · Cited by 87 · see citing works
Vav Proteins in Neutrophils Are Required for FcγR-Mediated Signaling to Rac GTPases and Nicotinamide Adenine Dinucleotide Phosphate Oxidase Component p40(phox)
Utomo, A. R. H., Culleré, X., Glogauer, M., Swat, W., & Mayadas, T. N. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.9.6388 · Cited by 86 · see citing works
Self-citation
Vav proteins control MyD88-dependent oxidative burst
Miletic, A. V., Graham, D. B., Montgrain, V., Fujikawa, K., Kloeppel, T., Brim, K. L., Weaver, B., Schreiber, R. D., Xavier, R. J., & Swat, W. (2006) · Blood · doi:10.1182/blood-2006-07-033662 · Cited by 84 · see citing works
Self-citation
SLP-76 Regulates Fcγ Receptor and Integrin Signaling in Neutrophils
Newbrough, S. A., Mócsai, A., Clemens, R. A., Wu, J. N., Silverman, M. A., Singer, A. L., Lowell, C. A., & Koretzky, G. A. (2003) · Immunity · doi:10.1016/s1074-7613(03)00305-4 · Cited by 82 · see citing works
The Hemopoietic Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates N -Formyl-Methionyl-Leucyl-Phenylalanine-Activated Neutrophil Functions
Kim, C., Marchal, C. C., Penninger, J. M., & Dinauer, M. C. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.8.4425 · Cited by 81 · see citing works
Gene therapy for chronic granulomatous disease
Barese, C. N., Goebel, W. S., & Dinauer, M. C. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.9.1423 · Cited by 73 · see citing works
Nosocomial Infections Surveillance
Brachman, P. S. (1993) · Infection Control and Hospital Epidemiology · doi:10.1086/646714 · Cited by 70 · see citing works
The Rac Effector p67phox Regulates Phagocyte NADPH Oxidase by Stimulating Vav1 Guanine Nucleotide Exchange Activity
Ming, W., Li, S., Billadeau, D. D., Quilliam, L. A., & Dinauer, M. C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00985-06 · Cited by 61 · see citing works
Rac2 Regulates Neutrophil Chemotaxis, Superoxide Production, and Myeloid Colony Formation through Multiple Distinct Effector Pathways
Carstanjen, D., 山内, 明., Koornneef, A., Zang, H., Filippi, M., Harris, C. E., Towe, J., Atkinson, S. J., Zheng, Y., Dinauer, M. C., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.4613 · Cited by 61 · see citing works
Gene therapy for chronic granulomatous disease
Kume, A., & Dinauer, M. C. (2000) · Journal of Laboratory and Clinical Medicine · doi:10.1067/mlc.2000.104458 · Cited by 52 · see citing works
Impaired NADPH oxidase activity in Rac2-deficient murine neutrophils does not result from defective translocation of p47phox and p67phox and can be rescued by exogenous arachidonic acid
Kim, C., & Dinauer, M. C. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0705371 · Cited by 49 · see citing works
PRAM-1 Is Required for Optimal Integrin-Dependent Neutrophil Function
Clemens, R. A., Newbrough, S. A., Chung, E. Y., Gheith, S. M. F., Singer, A. L., Koretzky, G. A., & Peterson, E. J. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10923-10932.2004 · Cited by 29 · see citing works
Loss of SLP-76 Expression within Myeloid Cells Confers Resistance to Neutrophil-Mediated Tissue Damage while Maintaining Effective Bacterial Killing
Clemens, R. A., Lenox, L. E., Kambayashi, T., Bezman, N., Maltzman, J. S., Nichols, K. E., & Koretzky, G. A. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4606 · Cited by 24 · see citing works
Factors affecting the course and severity of transnasally induced Staphylococcus aureus pneumonia in mice
Kimura, K., Miyazaki, S., Tateda, K., Matsumoto, T., TSUJIMOTO, S., & Yamaguchi, K. (1999) · Journal of Medical Microbiology · doi:10.1099/00222615-48-11-1005 · Cited by 16 · see citing works
Synergistic activation of PKD by the B cell antigen receptor and CD19 requires PI3K, Vav1 and PLCγ
Vigorito, E., Kövesdi, D., & Turner, M. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.11.008 · Cited by 13 · see citing works
Antigen receptor signaling: the Tuscan chronicles
Baldari, C. T., Koretzky, G. A., Telford, J. L., & Acuto, O. (2004) · Nature Immunology · doi:10.1038/ni0105-3 · Cited by 4 · see citing works

Flagged first, then by citations

Sorted by citations

Neutrophils to the ROScue: Mechanisms of NADPH oxidase activation and bacterial resistance
Nguyen, G. T., Green, E. R., & Mecsas, J. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00373 · Cited by 741 · see citing works
Neutrophils as emerging therapeutic targets
Németh, T., Sperandio, M., & Mócsai, A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0054-z · Cited by 657 · see citing works
Neutrophil cell surface receptors and their intracellular signal transduction pathways
Futosi, K., Fodor, S., & Mócsai, A. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.06.034 · Cited by 642 · see citing works
Are Reactive Oxygen Species Always Detrimental to Pathogens?
Paiva, C. N., & Bozza, M. T. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5447 · Cited by 559 · see citing works
The Ins and Outs of Leukocyte Integrin Signaling
Abram, C. L., & Lowell, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132554 · Cited by 535 · see citing works
The role of calcium signaling in phagocytosis
Nunes, P., & Demaurex, N. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.0110028 · Cited by 239 · see citing works
NOX2-dependent regulation of inflammation
Singel, K. L., & Segal, B. H. (2016) · Clinical Science · doi:10.1042/cs20150660 · Cited by 214 · see citing works
Integrin signalling and function in immune cells
Zhang, Y., & Wang, H. (2012) · Immunology · doi:10.1111/j.1365-2567.2011.03549.x · Cited by 207 · see citing works
The role of neutrophils in autoimmune diseases
Németh, T., & Mócsai, A. (2012) · Immunology Letters · doi:10.1016/j.imlet.2012.01.013 · Cited by 197 · see citing works
Reprint of Neutrophil cell surface receptors and their intracellular signal transduction pathways
Futosi, K., Fodor, S., & Mócsai, A. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.11.010 · Cited by 197 · see citing works
Lupus-associated causal mutation in neutrophil cytosolic factor 2 (NCF2) brings unique insights to the structure and function of NADPH oxidase
Jacob, C. O., Eisenstein, M., Dinauer, M. C., Ming, W., Liu, Q., John, S. K., Quismorio, F. P., Reiff, A. O., Myones, B. L., Kaufman, K. M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113251108 · Cited by 184 · see citing works
Tyrosine kinase Btk regulates E-selectin–mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) γ2 and PI3Kγ pathways
Mueller, H., Stadtmann, A., Van Aken, H., Hirsch, E., Wang, D., Ley, K., & Zarbock, A. (2010) · Blood · doi:10.1182/blood-2009-11-254185 · Cited by 164 · see citing works
Receptor Activation of NADPH Oxidases
Petry, A., Weitnauer, M., & Görlach, A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.3026 · Cited by 162 · see citing works
Intracellular signalling during neutrophil recruitment
Mócsai, A., Walzog, B., & Lowell, C. A. (2015) · Cardiovascular Research · doi:10.1093/cvr/cvv159 · Cited by 160 · see citing works
Role of phospholipase Cε in physiological phosphoinositide signaling networks
Smrcka, A. V., Brown, J. H., & Holz, G. G. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.009 · Cited by 153 · see citing works
Deciphering mechanisms of staphylococcal biofilm evasion of host immunity
Hanke, M. L., & Kielian, T. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00062 · Cited by 151 · see citing works
Calcium signalling and related ion channels in neutrophil recruitment and function
Immler, R., Simon, S. I., & Sperandio, M. (2018) · European Journal of Clinical Investigation · doi:10.1111/eci.12964 · Cited by 150 · see citing works
Regulation of innate immunity by NADPH oxidase
Segal, B. H., Grimm, M. J., Khan, A. N. H., Han, W., & Blackwell, T. S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.04.022 · Cited by 139 · see citing works
Activation of an Immunoregulatory and Antiviral Gene Expression Program in Poly(I:C)-Transfected Human Neutrophils
Tamassia, N., Moigne, V. L., Rossato, M., Donini, M., McCartney, S. A., Calzetti, F., Colonna, M., Bazzoni, F., & Cassatella, M. A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.9.6563 · Cited by 122 · see citing works
Critical role of phospholipase Cγ2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis
Jakus, Z., Simon, E., Frommhold, D., Sperandio, M., & Mócsai, A. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081859 · Cited by 119 · see citing works
NETosis and NADPH oxidase: at the intersection of host defense, inflammation, and injury
Almyroudis, N. G., Grimm, M. J., Davidson, B. A., Röhm, M., Urban, C. F., & Segal, B. H. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00045 · Cited by 119 · see citing works
Neutrophil-specific deletion of Syk kinase results in reduced host defense to bacterial infection
Ziffle, J. V., & Lowell, C. A. (2009) · Blood · doi:10.1182/blood-2009-05-220806 · Cited by 115 · see citing works
The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration
Jackson, J. T., Mulazzani, E., Nutt, S. L., & Masters, S. L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100905 · Cited by 113 · see citing works
“In addition to FcR signaling requiring PLCγ2 for efficient ROS production in murine neutrophils, PLCγ2 is also essential for postintegrin signaling induction of ROS, as well as being critical for the neutrophil-dependent host defense against bacterial infections in vivo (80).”
Background
Myeloperoxidase: Bridging the gap in neurodegeneration
Ray, R. S., & Katyal, A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.031 · Cited by 114 · see citing works
Immunology of chronic low-grade inflammation: relationship with metabolic function
van de Vyver, M. (2023) · Journal of Endocrinology · doi:10.1530/joe-22-0271 · Cited by 112 · see citing works
Chemokines, selectins and intracellular calcium flux: temporal and spatial cues for leukocyte arrest
Dixit, N., & Simon, S. I. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00188 · Cited by 108 · see citing works
Sialoglycoproteins adsorbed by <i>Pseudomonas aeruginosa</i> facilitate their survival by impeding neutrophil extracellular trap through siglec-9
Khatua, B., Bhattacharya, K., & Mandal, C. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0511260 · Cited by 104 · see citing works
Armed for destruction: formation, function and trafficking of neutrophil granules
Yin, C., & Heit, B. (2017) · Cell and Tissue Research · doi:10.1007/s00441-017-2731-8 · Cited by 96 · see citing works
The Regulatory Effects of Interleukin-4 Receptor Signaling on Neutrophils in Type 2 Immune Responses
Egholm, C., Heeb, L. E. M., Impellizzieri, D., & Boyman, O. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02507 · Cited by 91 · see citing works
Physiological and pathophysiological functions of SOCE in the immune system
Feske, S. (2012) · Frontiers in Bioscience-Elite · doi:10.2741/e540 · Cited by 91 · see citing works
P-Rex and Vav Rac-GEFs in platelets control leukocyte recruitment to sites of inflammation
Pan, D., Amison, R. T., Riffo‐Vasquez, Y., Spina, D., Cleary, S. J., Wakelam, M. J. O., Page, C. P., Pitchford, S. C., & Welch, H. C. E. (2014) · Blood · doi:10.1182/blood-2014-07-591040 · Cited by 89 · see citing works
Feedback Amplification of Neutrophil Function
Németh, T., & Mócsai, A. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.04.002 · Cited by 87 · see citing works
CD8+ T Cells Regulate Bone Tumor Burden Independent of Osteoclast Resorption
Zhang, K., Kim, S., Cremasco, V., Hirbe, A. C., Novack, D. V., Weilbaecher, K. N., & Faccio, R. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3922 · Cited by 82 · see citing works
Self-citation
NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex
Kim, E. Y., Anderson, M., Wilson, C., Hagmann, H., Benzing, T. R., & Dryer, S. E. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00191.2013 · Cited by 80 · see citing works
P-Rex1 and Vav1 Cooperate in the Regulation of Formyl-Methionyl-Leucyl-Phenylalanine–Dependent Neutrophil Responses
Lawson, C. D., Donald, S., Anderson, K. E., Patton, D. T., & Welch, H. C. E. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002738 · Cited by 78 · see citing works
Protein Kinase C Isoforms in Neutrophil Adhesion and Activation
Bertram, A., & Ley, K. F. (2011) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-011-0112-7 · Cited by 78 · see citing works
Phosphodiesterase 2 Mediates Redox-Sensitive Endothelial Cell Proliferation and Angiogenesis by Thrombin via Rac1 and NADPH Oxidase 2
Diebold, I., Djordjevic, T., Petry, A., Hatzelmann, A., Tenor, H., Hess, J., & Görlach, A. (2009) · Circulation Research · doi:10.1161/circresaha.109.196592 · Cited by 75 · see citing works
Identifying Yersinia YopH-Targeted Signal Transduction Pathways that Impair Neutrophil Responses during In Vivo Murine Infection
Rolán, H. G., Durand, E., & Mecsas, J. C. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.08.013 · Cited by 74 · see citing works
Wound healing defect of Vav3−/− mice due to impaired β2-integrin–dependent macrophage phagocytosis of apoptotic neutrophils
Sindrilaru, A., Peters, T., Schymeinsky, J., Oreshkova, T., Wang, H., Gompf, A., Mannella, F., Wlaschek, M., Sunderkötter, C., Rudolph, K. L., et al. (2009) · Blood · doi:10.1182/blood-2008-07-166702 · Cited by 73 · see citing works
Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice
Ow, C. P. C., Trask-Marino, A. L., Betrie, A. H., Evans, R. G., May, C. N., & Lankadeva, Y. R. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173798 · Cited by 72 · see citing works
Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations
Mebarek, S., Abousalham, A., Magne, D., Do, L.-D., Bandorowicz‐Pikuła, J., Pikuła, S., & Buchet, R. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14035036 · Cited by 69 · see citing works
Physiological and pathophysiological functions of SOCE in the immune system
Patrick, J. S. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/540 · Cited by 71 · see citing works
Tyrosine kinase signaling pathways in neutrophils
Futosi, K., & Mócsai, A. (2016) · Immunological Reviews · doi:10.1111/imr.12455 · Cited by 70 · see citing works
Store-operated calcium entry in thrombosis and thrombo-inflammation
Mammadova‐Bach, E., Nagy, M., Heemskerk, J. W. M., Nieswandt, B., & Braun, A. (2018) · Cell Calcium · doi:10.1016/j.ceca.2018.11.005 · Cited by 70 · see citing works
TRPC3-mediated Ca2+ influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts
Kitajima, N., Watanabe, K., Morimoto, S., Sato, Y., Kiyonaka, S., Hoshijima, M., Ikeda, Y., Nakaya, M., Ide, T., Mori, Y., et al. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.04.124 · Cited by 69 · see citing works
Lipid Signaling in T-Cell Development and FunctionPreprint
Huang, Y. H., & Sauer, K. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a002428 · Cited by 65 · see citing works
Class IA Phosphoinositide 3-Kinase β and δ Regulate Neutrophil Oxidase Activation in Response to Aspergillus fumigatus Hyphae
Boyle, K. B., Győri, D., Sindrilaru, A., Scharffetter‐Kochanek, K., Taylor, P. R., Mócsai, A., Stephens, L., & Hawkins, P. T. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002268 · Cited by 64 · see citing works
NETosis as a Pathogenic Factor for Heart Failure
Ling, S., & Xu, J. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6687096 · Cited by 64 · see citing works
NADPH Oxidases in Redox Regulation of Cell Adhesion and Migration
Schröder, K. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5633 · Cited by 60 · see citing works
Oleanolic acid acetate inhibits osteoclast differentiation by downregulating PLCγ2–Ca2+-NFATc1 signaling, and suppresses bone loss in mice
Kim, J., Cheon, Y., Oh, H. M., Rho, M., Erkhembaatar, M., Kim, M. S., Lee, C. H., Kim, J. J., Choi, M. K., Yoon, K., et al. (2013) · Bone · doi:10.1016/j.bone.2013.12.013 · Cited by 58 · see citing works
cAMP Signaling of Adenylate Cyclase Toxin Blocks the Oxidative Burst of Neutrophils through Epac-Mediated Inhibition of Phospholipase C Activity
Černý, O., Anderson, K. E., Stephens, L., Hawkins, P. T., & Šebo, P. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1601309 · Cited by 55 · see citing works
The Innate Immune Response toSalmonella entericaSerovar Typhimurium by Macrophages Is Dependent on TREM2-DAP12
Charles, J. F., Humphrey, M. B., Zhao, X., Quarles, E. K., Nakamura, M. C., Aderem, A. A., Seaman, W. E., & Smith, K. D. (2008) · Infection and Immunity · doi:10.1128/iai.00115-08 · Cited by 54 · see citing works
An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program
Tasseff, R. A., Jensen, H. A., Congleton, J., Dai, D. L., Rogers, K. V., Sagar, A., Bunaciu, R. P., Yen, A., & Varner, J. D. (2017) · Scientific Reports · doi:10.1038/s41598-017-14523-5 · Cited by 54 · see citing works
Phospholipase Cγ2 (PLCγ2) Is Key Component in Dectin-2 Signaling Pathway, Mediating Anti-fungal Innate Immune Responses
Gorjestani, S., Yu, M., Tang, B., Zhang, D., Wang, D., & Lin, X. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.307389 · Cited by 52 · see citing works
Vav/Phospholipase Cγ2–mediated control of a neutrophil‐dependent murine model of rheumatoid arthritis
Cremasco, V., Graham, D. B., Novack, D. V., Swat, W., & Faccio, R. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23757 · Cited by 51 · see citing works
Self-citation
Rac‐ GTP ases and Rac‐ GEF s in neutrophil adhesion, migration and recruitment
Pantarelli, C., & Welch, H. C. E. (2018) · European Journal of Clinical Investigation · doi:10.1111/eci.12939 · Cited by 48 · see citing works
Plasma glutamate–modulated interaction of A2AR and mGluR5 on BMDCs aggravates traumatic brain injury–induced acute lung injury
Dai, S.-S., Wang, H., Yang, N., An, J.-H., Li, W., Ning, Y., Zhu, P.-F., Chen, J., & Zhou, Y. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20122196 · Cited by 48 · see citing works
Neutrophil-Dependent Immunity During Pulmonary Infections and Inflammations
Effah, C. Y., Drokow, E. K., Agboyibor, C., Ding, L., He, S., Liu, S., Akorli, S. Y., Nuamah, E., Sun, T., Zhou, X., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.689866 · Cited by 48 · see citing works
Vav Protein Guanine Nucleotide Exchange Factor Regulates CD36 Protein-mediated Macrophage Foam Cell Formation via Calcium and Dynamin-dependent Processes
Rahaman, S. O., Zhou, G., & Silverstein, R. L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.265082 · Cited by 47 · see citing works
Vav Family Rho Guanine Nucleotide Exchange Factors Regulate CD36-mediated Macrophage Foam Cell Formation
Rahaman, S. O., Swat, W., Febbraio, M., & Silverstein, R. L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.192450 · Cited by 47 · see citing works
Self-citation
Immune and vascular dysfunction in diabetic wound healing
Ahmed, A. S., & Antonsen, E. (2016) · Journal of Wound Care · doi:10.12968/jowc.2016.25.sup7.s35 · Cited by 43 · see citing works
Role of Sphingomyelin Synthase in Controlling the Antimicrobial Activity of Neutrophils against Cryptococcus neoformans
Qureshi, A., Subathra, M., Grey, A., Schey, K., Del Poeta, M., & Luberto, C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015587 · Cited by 41 · see citing works
Phospholipase C Gamma 2 Is Critical for Development of a Murine Model of Inflammatory Arthritis by Affecting Actin Dynamics in Dendritic Cells
Cremasco, V., Benasciutti, E., Cella, M., Kisseleva, M. V., Croke, M., & Faccio, R. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008909 · Cited by 39 · see citing works
Self-citation
Lipid and Protein Co-Regulation of PI3K Effectors Akt and Itk in Lymphocytes
Wang, X., Hills, L. B., & Huang, Y. H. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00117 · Cited by 38 · see citing works
Class I Phosphoinositide-3-Kinases and Src Kinases Play a Nonredundant Role in Regulation of Adhesion-Independent and -Dependent Neutrophil Reactive Oxygen Species Generation
Fumagalli, L., Campa, C. C., Germena, G., Lowell, C. A., Hirsch, E., & Berton, G. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201951 · Cited by 39 · see citing works
Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst
Graham, D. B., Becker, C., Doan, A., Goel, G., Villablanca, E. J., Knights, D., Mok, A., Ng, A., Doench, J. G., Root, D. E., et al. (2015) · Nature Communications · doi:10.1038/ncomms8838 · Cited by 36 · see citing works
Self-citation
Roles of Phospholipase C Isozymes in Organogenesis and Embryonic Development
Nakamura, Y., & Fukami, K. (2009) · Physiology · doi:10.1152/physiol.00031.2009 · Cited by 36 · see citing works
Guanine nucleotide exchange factor Vav1 regulates perivascular homing and bone marrow retention of hematopoietic stem and progenitor cells
Sánchez‐Aguilera, A., Lee, Y. J., Celso, C. L., Ferraro, F., Brumme, K. M., Mondal, S., Kim, C., Dorrance, A. M., Luo, H. R., Scadden, D. T., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102018108 · Cited by 35 · see citing works
Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A2A Receptor Signaling
Li, J., Zhao, L., Xie, H., Zeng, Y., & Dai, S.-S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059257 · Cited by 34 · see citing works
SKAP2 is required for defense against K. pneumoniae infection and neutrophil respiratory burst
Nguyen, G. T., Shaban, L., Mack, M., Swanson, K. D., Bunnell, S. C., Sykes, D. B., & Mecsas, J. C. (2020) · eLife · doi:10.7554/elife.56656 · Cited by 33 · see citing works
Phospholipase Cγ2 is required for basal but not oestrogen deficiency–induced bone resorption
Kertész, Z., Győri, D., Körmendi, S., Fekete, T., Kis‐Tóth, K., Jakus, Z., Schett, G. A., Rajnavölgyi, É., Dobó‐Nagy, C., & Mócsai, A. (2011) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2011.02556.x · Cited by 33 · see citing works
Fast and furious: The neutrophil and its armamentarium in health and disease
Metzemaekers, M., Malengier‐Devlies, B., Gouwy, M., Somer, L. D., Cunha, F. Q., Opdenakker, G., & Proost, P. (2023) · Medicinal Research Reviews · doi:10.1002/med.21958 · Cited by 29 · see citing works
ITAM Signaling by Vav Family Rho Guanine Nucleotide Exchange Factors Regulates Interstitial Transit Rates of Neutrophils In Vivo
Graham, D. B., Zinselmeyer, B. H., Mascarenhas, F., Delgado, R. N., Miller, M. J., & Swat, W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004652 · Cited by 32 · see citing works
Self-citation
Sialic acids siglec interaction: a unique strategy to circumvent innate immune response by pathogens.
Khatua, B., Roy, S., & Mandal, C. (2013) · Europe PMC (PubMed Central) · Cited by 32 · see citing works
Myeloperoxidase: a new target for the treatment of stroke?
Pan, Y., Zhang, Y., Wang, Y.-C., Lu, Y., Huang, X., Lao, Y., Zhang, L., Yang, J., Shi, M., & Ma, H.-L. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.332130 · Cited by 31 · see citing works
Small GTPases and their guanine-nucleotide exchange factors and GTPase-activating proteins in neutrophil recruitment
Baker, M. J., Pan, D., & Welch, H. C. E. (2015) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000199 · Cited by 27 · see citing works
Yersinia pseudotuberculosis YopH targets SKAP2-dependent and independent signaling pathways to block neutrophil antimicrobial mechanisms during infection
Shaban, L., Nguyen, G. T., Mecsas-Faxon, B., Swanson, K. D., Tan, S., & Mecsas, J. C. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008576 · Cited by 28 · see citing works
Immunopathologies linked to integrin signalling
Wang, H., Lim, D., & Rudd, C. E. (2010) · Seminars in Immunopathology · doi:10.1007/s00281-010-0202-3 · Cited by 28 · see citing works
EsiB, a Novel Pathogenic Escherichia coli Secretory Immunoglobulin A-Binding Protein Impairing Neutrophil Activation
Pastorello, I., Paccani, S. R., Rosini, R., Mattera, R., Ferrer‐Navarro, M., Urosev, D., Nesta, B., Surdo, P. L., Vecchio, M. D., Rippa, V., et al. (2013) · mBio · doi:10.1128/mbio.00206-13 · Cited by 28 · see citing works
Cecal Ligation and Puncture Followed by Methicillin-Resistant Staphylococcus aureus Pneumonia Increases Mortality in Mice and Blunts Production of Local and Systemic Cytokines
Jung, E., Perrone, E. E., Liang, Z., Breed, E. R., Dominguez, J. A., Clark, A. T., Fox, A. C., Dunne, W. M., Burd, E. M., Farris, A. B., et al. (2011) · Shock · doi:10.1097/shk.0b013e3182360faf · Cited by 28 · see citing works
Self-citation
Conditional knockout of hypoxia-inducible factor 1-alpha in tumor-infiltrating neutrophils protects against pancreatic ductal adenocarcinoma
Sieow, J. L., Penny, H. L., Gun, S. Y., Tan, L. Q., Duan, K., Yeong, J. P. S., Pang, A., Lim, D., Toh, H. C., Lim, T. K. H., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010753 · Cited by 27 · see citing works
Comparison of Brazilian Plants Used to Treat Gastritis on the Oxidative Burst of Helicobacter pylori -Stimulated Neutrophil
Bonacorsi, C., da Fonseca, L. M., Raddi, M. S. G., Kitagawa, R. R., & Vilegas, W. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/851621 · Cited by 27 · see citing works
Inflammatory ER stress responses dictate the immunopathogenic progression of systemic candidiasis
Awasthi, D., Chopra, S., Cho, B. A., Emmanuelli, A., Sandoval, T., Hwang, S., Chae, C.-S., Salvagno, C., Tan, C., Vasquez-Urbina, L., et al. (2022) · bioRxiv · doi:10.1172/jci167359 · Cited by 20 · see citing works
Soluble Regulatory Proteins for Activation of NOX Family NADPH Oxidases
Sumimoto, H., Minakami, R., & Miyano, K. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9424-3_8 · Cited by 23 · see citing works
PLCγ2: where bone and immune cells find their common ground
Faccio, R., & Cremasco, V. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05217.x · Cited by 21 · see citing works
Self-citation
Phospholipase C Activator m-3M3FBS Protects against Morbidity and Mortality Associated with Sepsis
Kim, S. D., Kim, H. J., Shim, J. W., Lee, H. Y., Lee, S. K., Kwon, S., Jung, Y. S., Baek, S., Park, J. S., Zabel, B. A., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200635 · Cited by 20 · see citing works
From Cytokines to Biomarkers: Mapping the Immunopathology of Inflammatory Bowel Disease
Baum, S., Hamedi, K. R., Loftus, C., Loftus, G., Zhou, E.-R., & Arce, S. (2025) · Cells · doi:10.3390/cells14201589 · Cited by 18 · see citing works
Roscovitine enhances all-trans retinoic acid (ATRA)-induced nuclear enrichment of an ensemble of activated signaling molecules and augments ATRA-induced myeloid cell differentiation
Rashid, A., Duan, X., Gao, F., Yang, M., & Yen, A. (2020) · Oncotarget · doi:10.18632/oncotarget.27508 · Cited by 18 · see citing works
Phospholipase Cγ1 (PLCγ1) Controls Osteoclast Numbers via Colony-stimulating Factor 1 (CSF-1)-dependent Diacylglycerol/β-Catenin/CyclinD1 Pathway
Yang, Z., Kim, S., Mahajan, S., Zamani, A., & Faccio, R. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.764928 · Cited by 17 · see citing works
Self-citation
PLC γ2 promotes apoptosis while inhibits proliferation in rat hepatocytes through PKCD / JNK MAPK and PKCD /p38 MAPK signalling
Chen, X., Lv, Q., Ma, J., & Liu, Y. (2018) · Cell Proliferation · doi:10.1111/cpr.12437 · Cited by 16 · see citing works
Osteopetrosis with micro-lacunar resorption because of defective integrin organization
Blair, H. C., Yaroslavskiy, B. B., Robinson, L. J., Mapara, M. Y., Pangrazio, A., Guo, L., Chen, K., Vezzoni, P., Tolar, J., & Orchard, P. J. (2009) · Laboratory Investigation · doi:10.1038/labinvest.2009.58 · Cited by 16 · see citing works
ITAM signaling in dendritic cells controls T helper cell priming by regulating MHC class II recycling
Graham, D. B., Akilesh, H. M., Gmyrek, G. B., Piccio, L. M., Gilfillan, S., Sim, J. E., Belizaire, R., Carrero, J. A., Wang, Y., Blaufuss, G. S., et al. (2010) · Blood · doi:10.1182/blood-2009-10-250415 · Cited by 16 · see citing works
Self-citation
Roscovitine enhances All-trans retinoic acid (ATRA)-induced leukemia cell differentiation: Novel effects on signaling molecules for a putative Cdk2 inhibitor
Rashid, A., Duan, X., Gao, F., Yang, M., & Yen, A. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109555 · Cited by 13 · see citing works
Restoration of Responsiveness of Phospholipase Cγ2-Deficient Platelets by Enforced Expression of Phospholipase Cγ1
Zheng, Y., Adams, T. L., Zhi, H., Yu, M., Wen, R., Newman, P. J., Wang, D., & Newman, D. K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119739 · Cited by 13 · see citing works
Redox homeostasis and therapeutic modulation: the central role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) activation in systemic diseases and reproductive dysfunction
Kumar, A., & Ramanarayanan, S. (2025) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2025-0153 · Cited by 12 · see citing works
Vav1
Bustelo, X. R. (2010) · AfCS-Nature Molecule Pages · doi:10.1038/mp.a002360.01 · Cited by 12 · see citing works
Dock2 generates characteristic spatiotemporal patterns of Rac activity to regulate neutrophil polarisation, migration and phagocytosis
Machin, P. A., Johnsson, A., Massey, E. J., Pantarelli, C., Chetwynd, S. A., Chu, J. Y., Okkenhaug, H., Segonds-Pichon, A., Walker, S. A., Malliri, A., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1180886 · Cited by 11 · see citing works
Immune Complexes Isolated from Patients with Pulmonary Tuberculosis Modulate the Activation and Function of Normal Granulocytes
Senbagavalli, P., Hilda, J. N., Ramanathan, V. D., Kumaraswami, V., Nutman, T. B., & Babu, S. (2012) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00437-12 · Cited by 11 · see citing works
The Rac-GEF Tiam1 controls integrin-dependent neutrophil responses
Hornigold, K., Baker, M. J., Machin, P. A., Chetwynd, S. A., Johnsson, A., Pantarelli, C., Islam, P., Stammers, M., Crossland, L., Oxley, D., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1223653 · Cited by 10 · see citing works
Phospholipase Cγ2 Is Essential for Experimental Models of Epidermolysis Bullosa Acquisita
Szilveszter, K. P., Vikár, S., Horváth, Á. I., Helyes, Z., Sárdy, M., & Mócsai, A. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2021.09.019 · Cited by 10 · see citing works

Vav Proteins in Neutrophils Are Required for FcγR-Mediated Signaling to Rac GTPases and Nicotinamide Adenine Dinucleotide Phosphate Oxidase Component p40(phox)
Utomo, A. R. H., Culleré, X., Glogauer, M., Swat, W., & Mayadas, T. N. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.9.6388 · Cited by 86 · see citing works
Self-citation
Neutrophils from p40phox−/− mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing
Ellson, C. D., Davidson, K., Ferguson, G., O'Connor, R. P., Stephens, L., & Hawkins, P. T. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052069 · Cited by 182 · see citing works
Vav proteins control MyD88-dependent oxidative burst
Miletic, A. V., Graham, D. B., Montgrain, V., Fujikawa, K., Kloeppel, T., Brim, K. L., Weaver, B., Schreiber, R. D., Xavier, R. J., & Swat, W. (2006) · Blood · doi:10.1182/blood-2006-07-033662 · Cited by 84 · see citing works
Self-citation
Intersecting Stories of the Phagocyte NADPH Oxidase and Chronic Granulomatous Disease
Nauseef, W. M., & Clark, R. A. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9424-3_1 · Cited by 22 · see citing works
RhoG Regulates the Neutrophil NADPH Oxidase
Condliffe, A. M., Webb, L. M. C., Ferguson, G., Davidson, K., Turner, M., Vigorito, E., Manifava, M., Chilvers, E. R., Stephens, L., & Hawkins, P. T. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.9.5314 · Cited by 43 · see citing works

Authors: Graham, D. B., Robertson, C. M., Bautista, J., Mascarenhas, F., Diacovo, M. J., Montgrain, V., Lam, S. K., Cremasco, V., Dunne, W. M., Faccio, R., Coopersmith, C. M., & Swat, W.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Swat, Wojciech
ORCID: Graham, Daniel B.
Bautista, Jhoanne
Diacovo, M. Julia
Cremasco, Viviana
Dunne, W. Michael
Faccio, Roberta
Coopersmith, Craig M.
Swat, Wojciech
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2007-11-01
Volume: 117
Issue: 11
Pages: 3445-3452
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci32729
PMC: PMC2000813
OpenAlex: W1987998552
Cited by: 124
References: 55
Citations by year: 2026: 4 · 2025: 3 · 2024: 4 · 2023: 7 · 2021: 8 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 5 · 2014: 4 · 2013: 15 · 2012: 10
FWCI: 3.10
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
Funders: National Institutes of Health (GM072808)
National Cancer Institute (T32CA009547)
National Institute of General Medical Sciences (R01GM072808, GM 072808, GM66202, R01GM066202)
National Institute of Allergy and Infectious Diseases (AI 063024-02, AI-06107703)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Keywords: neutrophil respiratory burst, Vav, PLCγ2, NADPH oxidase, NOX2, integrin signaling, neutrophil adhesion, reactive oxygen species, chronic granulomatous disease, Staphylococcus aureus, Pseudomonas aeruginosa, diacylglycerol, intracellular calcium, host defense, nosocomial pneumonia
MeSH terms: Animals, Calcium, Cell Adhesion, Diglycerides, Granulomatous Disease, Chronic, Humans, Neutrophils, Pseudomonas Infections, Staphylococcal Infections, Signal Transduction, Respiratory Burst, Reactive Oxygen Species, Mice, Knockout, Pneumonia, Bacterial, Sepsis, NADPH Oxidases, Protein Subunits, Mice, Proto-Oncogene Proteins c-vav, Phospholipase C gamma

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCγ2 signaling axis in mice

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks