The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCγ2 signaling axis in mice
Open accessAbstract
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.
Overview
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
Cites
Statistics
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
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.
Citations
Cites
(2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200405-644st · Cited by 5,932
NOX enzymes and the biology of reactive oxygen
Lambeth, J. D. (2004) · Nature Reviews Immunology · doi:10.1038/nri1312 · Cited by 3,125
Neutrophils and immunity: challenges and opportunities
Nathan, C. (2006) · Nature reviews. Immunology · doi:10.1038/nri1785 · Cited by 2,971
System, A. R. F. T. N. (2003) · American Journal of Infection Control · doi:10.1016/j.ajic.2003.09.002 · Cited by 2,923
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
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
(1999) · American Journal of Infection Control · doi:10.1016/s0196-6553(99)70031-3 · Cited by 899
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
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
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
Research works printed but not linked: 1
- Williams, 2000, Blood., 96, 1646
Cited by
Sorted by citations
Items 101–124 of 124
Futosi, K., Kása, O., Szilveszter, K. P., & Mócsai, A. (2021) · Arthritis & Rheumatology · doi:10.1002/art.41704 · Cited by 10
IP3R function in cells of the immune system
Akimzhanov, A. M., & Boehning, D. F. (2011) · Wiley Interdisciplinary Reviews Membrane Transport and Signalling · doi:10.1002/wmts.27 · Cited by 10
Myeloperoxidase enzyme levels and oxidative stress in bipolar disorders
Aksoy, S. N., Saygılı, E. İ., Bülbül, F., Bahar, A. Y., SAVAS, H. A., Vini, O., Altındağ, A., Bayram, A., & Tarakçýolu, M. (2010) · AFRICAN JOURNAL OF BIOTECHNOLOGY · doi:10.5897/ajb2010.000-3181 · Cited by 10
Kasamatsu, A., Nozaki, R., Kawasaki, K., Saito, T., Minemura, C., Seki, N., Moss, J., & Uzawa, K. (2024) · Cancers · doi:10.3390/cancers16061242 · Cited by 5
“Superbugs Bunny” Outsmarts Our Immune Defense
Haebich, D., & von Nussbaum, F. (2008) · ChemMedChem · doi:10.1002/cmdc.200800171 · Cited by 5
Gu, Z., Liu, J.-Z., Fu, J., Lu, Y., Li, Q., Zou, Z.-M., Liu, J., Zuo, Z., Su, L., Tan, H., et al. (2025) · Burns & Trauma · doi:10.1093/burnst/tkae050 · Cited by 4
Abou-El-Naga, I. F. (2025) · Microbial Pathogenesis · doi:10.1016/j.micpath.2025.108267 · Cited by 4
Retinoic acid–driven expansion of CD16hiCD177+ neutrophils mediates steroid-resistant GI-GVHD
Liang, W., Xu, D., Zhang, L. F., Qu, Y., Li, L., Zhong, K., Meng, Y., Zhu, J., Wang, S., Tan, L., et al. (2026) · Blood · doi:10.1182/blood.2025032193 · Cited by 1
Evaluating the effect of a mild cycling heating period on leukocyte coping capacity in growing pigs
Byrd, C. J., & Young, J. M. (2023) · Frontiers in Animal Science · doi:10.3389/fanim.2023.1148218 · Cited by 1
El‐Lakany, M. A., Wedn, A. M., & El‐Mas, M. M. (2024) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-3-031-62131-4_9 · Cited by 1
Greenwood, H. L. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham) · Cited by 1
Regulation of NADPH Oxidases by Rac GTPase
Bokoch, G., Gianni, D., Kim, J., & Kao, Y.-Y. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00216-3
Phospo-PKCs in Abeta1-42-Specific Human T Cells from Alzheimer’s Disease Patients
Lanuti, P., Marchisio, M., Pierdomenico, L., & Miscia, S. (2011) · InTech eBooks · doi:10.5772/21160
Signal Inhibitory Receptor on Leukocytes-1 (SIRL-1), a potent regulator of neutrophil function
Avondt, K. V. (2014) · Utrecht University Repository (Utrecht University)
Suzuki, K., & Namiki, H. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23416
Regulation of leukocyte integrin binding to Ig-family ligands
Uotila, L. M. (2014) · Työväentutkimus Vuosikirja
Pathogens, infectious disease biology and sialic acid
Ghosh, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816126-5.00005-6
Phagoburst Response Level of Neutrophils to Septic and Non-Septic Acinetobacter baumannii Isolates
Elkhateeb, L., Yacoub, M. A., Bdour, S. M., & Shehabi, A. A. (2021) · The Open Microbiology Journal · doi:10.2174/1874285802115010016
Vav family exchange factors: Potential regulator in atherosclerosis
Zhang, Y., Ren, Y., Zhou, T., Qian, Z., & Bao, Z. (2024) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2024.101878
Antifungal peptides for biofilm disruption: Mechanisms, design strategies, and translational outlook
Saini, Y., Wani, M. Y., & Hameed, S. (2026) · Microbial Pathogenesis · doi:10.1016/j.micpath.2026.108601
A Master of Disguise: Disseminated Fungal Disease Revealing Immunodeficiency
Rajashekar, V., Akshaya Kumar, B., Hema, K., Senthil Priyan, K., Mukil, S., Anitha, A., Venisha, M., Adalarasan, S., Rachana, R., & Santhi, T. (2026) · Cureus · doi:10.7759/cureus.111953
Epigenetic Reactivation of Lineage Differentiation to Target LeukemiaPreprint
Amos, S. M., Chen, C.-C., Xiang, Y., Motoyama, K., González-Robles, T. J., Narendra, V. K., Johnson, G. A., Lee, H., Ho, Y.-J., Celikoyar, I., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.08.737260
Cryptococcus–Neutrophil Interaction
Qureshi, A., & Poeta, M. D. (2011) · Topics in current genetics · doi:10.1007/978-3-642-22916-9_13
Metadata
- 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
- Venue
- Journal of Clinical Investigation
- Published
- 2007-11-01
- Volume
- 117
- Issue
- 11
- Pages
- 3445-3452
- ISSN
- 0021-9738 (ISSN-L)
- 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
