Substance P inhibits natural killer cell cytotoxicity through the neurokinin-1 receptor
Open accessAbstract
SP is a potent neuroimmunomodulator that functions through ligating members of the neurokinin receptor family, one of which, NK1R, is widely expressed in immune cells. As in humans, circulating SP levels are increased in pathologic states associated with impairment of NK cell functions, such as depression and HIV infection, we hypothesized that SP has a direct, inhibitory effect upon NK cells. We have studied a clonal human NK cell line (YTS) as well as ex vivo human NK cells and have determined that truncated and full-length NK1R isoforms are expressed in and SP bound by ex vivo NK cells and the YTS NK cell line. Incubation of YTS cells with 10−6 M SP and ex vivo NK cells with 10−5 M SP inhibited cytotoxic ability by ∼20% and reduced degranulation. This inhibitory effect upon cytotoxicity was partially prevented by the NK1R antagonist CP96,345. The treatment of YTS or ex vivo NK cells with SP neither down-modulated NCR expression nor affected triggering receptor-induced NF-κB activation. Preincubation of YTS cells with SP, however, did abbreviate the typically prolonged intracellular calcium increase induced by target cell engagement and reduced triggering receptor-induced pERK. Thus, SP has the potential to regulate NK cell functions and acts downstream from neurokinin receptors to modulate NK cell activation signaling. This mechanism may contribute to impairment of NK cell function in certain disease states associated with increased circulating SP. Antagonism of this system may present an opportunity to augment NK cell function therapeutically in selected human diseases.
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SP inhibits NK cell cytotoxicity through NK1R.
“SP has been shown to inhibit NK cell cytotoxicity through NK1R79.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [79]
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NATURAL KILLER CELLS IN ANTIVIRAL DEFENSE: Function and Regulation by Innate Cytokines
Biron, C. A., Nguyen, K. B., Pien, G. C., Cousens, L. P., & Salazar‐Mather, T. P. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.189 · Cited by 2,110 · see citing works
Up on the tightrope: natural killer cell activation and inhibition
Lanier, L. L. (2008) · Nature Immunology · doi:10.1038/ni1581 · Cited by 1,656 · see citing works
The Relationship of Depression and Stressors to Immunological Assays: A Meta-Analytic Review
Zorrilla, E. P., Luborsky, L., McKay, J. R., Rosenthal, R., Houldin, A., Tax, A., McCorkle, R., Seligman, D. A., & Schmidt, K. (2001) · Brain, Behavior, and Immunity · doi:10.1006/brbi.2000.0597 · Cited by 995 · see citing works
Formation and function of the lytic NK-cell immunological synapse
Orange, J. S. (2008) · Nature reviews. Immunology · doi:10.1038/nri2381 · Cited by 613 · see citing works
Self-citationThe nervous system and innate immunity: the neuropeptide connection
Brogden, K. A., Guthmiller, J. M., Salzet, M., & ZASLOFF, M. A. (2005) · Nature Immunology · doi:10.1038/ni1209 · Cited by 445 · see citing works
DeFea, K., Vaughn, Z. D., O’Bryan, E., Nishijima, D., Déry, O., & Bunnett, N. W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190276697 · Cited by 405 · see citing works
Mavilio, D., Benjamin, J., Daucher, M., Lombardo, G., Kottilil, S., Planta, M. A., Marcenaro, E., Bottino, C., Moretta, L., Moretta, A., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336091100 · Cited by 386 · see citing works
Dowsey, A. W., English, J. A., Lisacek, F., Morris, J. Z., Yang, G.-Y., & Dunn, M. J. (2011) · Cited by 352 · see citing works
Hong, H. S., Lee, J., Lee, E., Kwon, Y. S., Lee, E., Ahn, W., Jiang, M. H., Kim, J. C., & Son, Y. (2009) · Nature Medicine · doi:10.1038/nm.1909 · Cited by 349 · see citing works
Human natural killer cell deficiencies and susceptibility to infection
Orange, J. S. (2002) · Microbes and Infection · doi:10.1016/s1286-4579(02)00038-2 · Cited by 339 · see citing works
Self-citationThe role of substance P in stress and anxiety responses
Ebner, K., & Singewald, N. (2006) · Amino Acids · doi:10.1007/s00726-006-0335-9 · Cited by 304 · see citing works
Wülfing, C., Sjaastad, M. D., & Davis, M. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6302 · Cited by 278 · see citing works
Substance P recognition by a subset of human T lymphocytes.
Payan, D. G., Brewster, D., Missirian-Bastian, A., & Goetzl, E. J. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111567 · Cited by 252 · see citing works
Sensory neuropeptides: their role in inflammation and wound healing
Brain, S. D. (1997) · Immunopharmacology · doi:10.1016/s0162-3109(97)00055-6 · Cited by 246 · see citing works
Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor.
Fong, T. M., Anderson, S. A., Yu, H., Huang, R. R., & Strader, C. D. (1992) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)08831-5 · Cited by 243 · see citing works
Human natural killer cell deficiencies
Orange, J. S. (2006) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0b013e3280106b65 · Cited by 229 · see citing works
Self-citationSubstance P induces TNF-α and IL-6 production through NFκB in peritoneal mast cells
Azzolina, A., Bongiovanni, A., & Lampiasi, N. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2003.09.003 · Cited by 196 · see citing works
Deficient natural killer cell cytotoxicity in patients with IKK-γ/NEMO mutations
Orange, J. S., Brodeur, S. R., Jain, A. K., Bonilla, F. A., Schneider, L. C., Kretschmer, R. R., Nurko, S., Rasmussen, W. L., Köhler, J. R., Gellis, S. E., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14858 · Cited by 194 · see citing works
Self-citationNK cells in HIV‐1 infection: evidence for their role in the control of HIV‐1 infection
Alter, G., & Altfeld, M. A. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2008.02045.x · Cited by 184 · see citing works
Deficient natural killer cell cytotoxicity in patients with IKK-γ/NEMO mutations
Orange, J. S., Brodeur, S. R., Jain, A., Bonilla, F. A., Schneider, L. C., Kretschmer, R. R., Nurko, S., Rasmussen, W. L., Köhler, J. R., Gellis, S. E., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214858 · Cited by 174 · see citing works
Self-citationSatake, H., & Kawada, T. (2006) · Current Drug Targets · doi:10.2174/138945006778019273 · Cited by 149 · see citing works
Cytokine Secretion Is Distinct from Secretion of Cytotoxic Granules in NK Cells
Reefman, E., Kay, J. G., Wood, S. M., Offenhäuser, C., Brown, D. L., Roy, S., Stanley, A. C., Low, P. C., Manderson, A. P., & Stow, J. L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0803954 · Cited by 144 · see citing works
Chen, X., Allan, D., Krzewski, K., Ge, B.-X., Kopcow, H. D., & Strominger, J. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604236103 · Cited by 126 · see citing works
Trotta, R., Puorro, K. A., Paroli, M., Azzoni, L., Abebe, B., Eisenlohr, L. C., & PERUSSIA, B. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.12.6648 · Cited by 116 · see citing works
Tachykinins and their Receptors in Human Malignancies
Palma, C. (2006) · Current Drug Targets · doi:10.2174/138945006778019282 · Cited by 107 · see citing works
Tyramide Signal Amplification Method in Multiple-Label Immunofluorescence Confocal Microscopy
Wang, G., Achim, C. L., Hamilton, R. L., Wiley, C. A., & Soontornniyomkij, V. (1999) · Methods · doi:10.1006/meth.1999.0813 · Cited by 106 · see citing works
Lai, J.-P., Lai, S., Tuluc, F., Tansky, M. F., Kilpatrick, L. E., Leeman, S. E., & Douglas, S. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806632105 · Cited by 105 · see citing works
Self-citationNeurokinin 1 receptor isoforms and the control of innate immunity
Tuluc, F., Lai, J. P., Kilpatrick, L. E., Evans, D. L., & Douglas, S. D. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.03.006 · Cited by 102 · see citing works
Self-citationSanborn, K. B., Rak, G. D., Maru, S. Y., Demers, K., DiFeo, A. V., Martignetti, J. A., Betts, M. R., Favier, R., Banerjee, P. P., & Orange, J. S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0804337 · Cited by 99 · see citing works
Self-citationLai, J.-P., Ho, W., Kilpatrick, L. E., Wang, X., Tuluc, F., Korchak, H. M., & Douglas, S. D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602563103 · Cited by 94 · see citing works
Self-citationGalea‐Lauri, J., Darling, D. C., Gan, S. U., Krivochtchapov, L., Kuiper, M., Gäken, J. A., Souberbielle, B. E., & Farzaneh, F. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.1.62 · Cited by 85 · see citing works
Do Substance P and the NK1 Receptor have a Role in Depression and Anxiety?
McLean, S. (2005) · Current Pharmaceutical Design · doi:10.2174/1381612053764779 · Cited by 85 · see citing works
Neurotransmitters regulate the migration and cytotoxicity in natural killer cells
Lang, K., Drell, T. L., Niggemann, B., Zänker, K. S., & Entschladen, F. (2003) · Immunology Letters · doi:10.1016/j.imlet.2003.09.004 · Cited by 85 · see citing works
An essential function for β-arrestin 2 in the inhibitory signaling of natural killer cells
Yu, M., Su, L., Zou, L., Liu, Y., Wu, N., Kong, L., Zhuang, Z., Sun, L., Liu, H., Hu, J., et al. (2008) · Nature Immunology · doi:10.1038/ni.1635 · Cited by 84 · see citing works
Substance P at the nexus of mind and body in chronic inflammation and affective disorders.
Rosenkranz, M. A. (2007) · Psychological Bulletin · doi:10.1037/0033-2909.133.6.1007 · Cited by 81 · see citing works
G protein-coupled receptors in natural killer cells
Maghazachi, A. A. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0103019 · Cited by 80 · see citing works
Natural killer cell functions mediated by the neuropeptide substance P
Feistritzer, C., Clausen, J., Sturn, D. H., Djanani, A. M., Gunsilius, E., Wiedermann, C. J., & Kähler, C. M. (2003) · Regulatory Peptides · doi:10.1016/s0167-0115(03)00193-9 · Cited by 79 · see citing works
Meshki, J., Douglas, S. D., Lai, J.-P., Schwartz, L., Kilpatrick, L. E., & Tuluc, F. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808825200 · Cited by 79 · see citing works
Self-citationChernova, I., Lai, J.-P., Li, H., Schwartz, L., Tuluc, F., Korchak, H. M., Douglas, S. D., & Kilpatrick, L. E. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0408260 · Cited by 79 · see citing works
Self-citationTominaga, K., Saito, S., Matsuura, M., & Nakano, M. (1999) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(99)00037-3 · Cited by 70 · see citing works
Evans, D. L., Lynch, K. G., Benton, T. D., Dubé, B., Gettes, D. R., Tustin, N. B., Lai, J. P., Metzger, D. S., & Douglas, S. D. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.08.012 · Cited by 69 · see citing works
Self-citationMathers, A. R., Tckacheva, O. A., Janelsins, B., Shufesky, W. J., Morelli, A. E., & Larregina, A. T. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.7006 · Cited by 67 · see citing works
Tachykinin receptor antagonists in clinical trials
Quartara, L., Altamura, M., Evangelista, S., & Maggi, C. A. (2009) · Expert Opinion on Investigational Drugs · doi:10.1517/13543780903379530 · Cited by 67 · see citing works
Substance P up-regulates macrophage inflammatory protein-1β expression in human T lymphocytes
Guo, C., Lai, J.-P., Luo, H.-M., Douglas, S. D., & Ho, W. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00277-1 · Cited by 64 · see citing works
Self-citationFunctional consequences of alteration of N-linked glycosylation sites on the neurokinin 1 receptor
Tansky, M. F., Pothoulakis, C., & Leeman, S. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703394104 · Cited by 64 · see citing works
Elevated substance P levels in HIV-infected men
Douglas, S. D., Ho, W., Gettes, D. R., Cnaan, A., Zhao, H., Leserman, J., Petitto, J. M., Golden, R. N., & Evans, D. L. (2001) · AIDS · doi:10.1097/00002030-200110190-00019 · Cited by 61 · see citing works
Self-citationTachykinin-mediated modulation of the immune response
Kenneth, L. B. (2004) · Frontiers in bioscience · doi:10.2741/1484 · Cited by 59 · see citing works
Tachykinins and Neuropsychiatric Disorders
Chahl, L. A. (2006) · Current Drug Targets · doi:10.2174/138945006778019309 · Cited by 59 · see citing works
The impact of c-met/scatter factor receptor on dendritic cell migration
Kurz, S. M., Diebold, S. S., Hieronymus, T., Gust, T. C., Bartůněk, P., Sachs, M., Birchmeier, W., & Zenke, M. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200207)32:7 · Cited by 58 · see citing works
Laniyonu, A. A., Sliwinski-Lis, E., & Fleming, N. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)80365-x · Cited by 52 · see citing works
Jin, Y., Knudsen, E., Wang, L., & Maghazachi, A. A. (2003) · European Journal of Immunology · doi:10.1002/eji.200323711 · Cited by 51 · see citing works
Alpha-defensins inhibit HIV infection of macrophages through upregulation of CC-chemokines
Guo, C., Tan, N., Song, L., Douglas, S. D., & Ho, W. (2004) · AIDS · doi:10.1097/00002030-200405210-00020 · Cited by 47 · see citing works
Self-citationSchmidlin, F., Roosterman, D., & Bunnett, N. W. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00541.2002 · Cited by 47 · see citing works
β-Arrestins: Multifunctional Cellular Mediators
Barki‐Harrington, L., & Rockman, H. A. (2008) · Physiology · doi:10.1152/physiol.00042.2007 · Cited by 46 · see citing works
Solovera, J. J., Alvarez-Mon, M., Casas, J., Carballido, J., & Durántez, A. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.139.3.876 · Cited by 45 · see citing works
Williams, R., Zou, X., & Hoyle, G. W. (2006) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00475.2005 · Cited by 42 · see citing works
Lai, J.-P., Douglas, S. D., Zhao, M., & Ho, W. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(99)00120-9 · Cited by 39 · see citing works
Self-citationNatural Killer Cell Enumeration and Function in HIV-Infected and High-Risk Uninfected Adolescents
Douglas, S. D., Durako, S. J., Tustin, N. B., Houser, J., Muenz, L. R., Starr, S. E., & Wilson, C. M. (2001) · AIDS Research and Human Retroviruses · doi:10.1089/08892220151126643 · Cited by 38 · see citing works
Self-citationRolin, J., Sand, K. L., Knudsen, E., & Maghazachi, A. A. (2009) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-009-0775-7 · Cited by 38 · see citing works
NKp30 Ligation Induces Rapid Activation of the Canonical NF-κB Pathway in NK Cells
Pandey, R., DeStephan, C. M., Madge, L. A., May, M. J., & Orange, J. S. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.11.7385 · Cited by 36 · see citing works
Self-citationTeng, J. M. C., Liu, X. R., Mills, G. B., & Dupont, B. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.9.3222 · Cited by 35 · see citing works
Detection of full-length and truncated neurokinin-1 receptor mRNA expression in human brain regions
Lai, J.-P., Cnaan, A., Zhao, H., & Douglas, S. D. (2007) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2007.10.004 · Cited by 34 · see citing works
Self-citationLagadari, M., Truta-Feles, K., Lehmann-Pohl, K., Berod, L., Ziemer, M., Idzko, M., Barz, D., Kamradt, T., Maghazachi, A. A., & Norgauer, J. (2009) · International Immunology · doi:10.1093/intimm/dxp035 · Cited by 32 · see citing works
Analysis of fluorescently labeled substance P analogs: binding, imaging and receptor activation
Bennett, V. J., & Simmons, M. A. (2001) · BMC Chemical Biology · doi:10.1186/1472-6769-1-1 · Cited by 31 · see citing works
Flageole, H., Senterman, M. K., & Trudel, J. L. (1992) · Journal of Surgical Research · doi:10.1016/0022-4804(92)90088-h · Cited by 27 · see citing works
Douglas, S. D., Cnaan, A., Lynch, K. G., Benton, T. D., Zhao, H., Gettes, D. R., & Evans, D. L. (2008) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2007.0207 · Cited by 25 · see citing works
Self-citationPlasma and cerebrospinal fluid substance P in post‐stroke patients with depression
Li, L., Gao, X., Zhao, J., Ji, X., Wei, H., & Luo, Y. (2009) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2009.01936.x · Cited by 20 · see citing works
Real-Time Reverse Transcription-PCR Quantitation of Substance P Receptor (NK-1R) mRNA
Lai, J.-P., Douglas, S. D., Wang, Y., & Ho, W. (2005) · Clinical and Vaccine Immunology · doi:10.1128/cdli.12.4.537-541.2005 · Cited by 20 · see citing works
Self-citationWest, M. A., Clair, L., Bellingham, J. M., Wahlstrom, K., & Rodriguez, J. L. (2000) · Shock · doi:10.1097/00024382-200014020-00016 · Cited by 19 · see citing works
Norgauer (1992) · International Journal of Oncology · doi:10.3892/ijo_00000151 · Cited by 19 · see citing works
Maghazachi, A. A., Knudsen, E., Jin, Y., Jenstad, M., & Chaudhry, F. A. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.06.027 · Cited by 17 · see citing works
Beerli, R. R., Bréard, J., Comisso, M., Bohuon, C., Pallardy, M. J., & Bertoglio, J. H. (1996) · Cellular Immunology · doi:10.1006/cimm.1996.0045 · Cited by 14 · see citing works
CD28‐dependent killing by human YT cells requires phosphatidylinositol 3‐kinase activation
Lu, Y., Rodriguez, R., Bjorndahl, J. M., Phillips, C. A., & Trevillyan, J. M. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260615 · Cited by 7 · see citing works
Flagged first, then by citations
1 of the 74 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [54]54. Kveberg L., Bryceson Y., Inngjerdingen M., Rolstad B., Maghazachi A. A. (2002) Sphingosine 1 phosphate induces the chemotaxis of human natural killer cells. Role for heterotrimeric G proteins and phosphoinositide 3 kinases. Eur. J. Immunol. 32, 1856–1864 [DOI] [PubMed] [Google Scholar]
Cited by
Sorted by citations
Role of Substance P Neuropeptide in Inflammation, Wound Healing, and Tissue Homeostasis
Suvas, S. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601751 · Cited by 350 · see citing works
Critical Neurotransmitters in the Neuroimmune Network
Hodo, T., de Aquino, M. T. P., Shimamoto, A., & Shanker, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01869 · Cited by 187 · see citing works
Oxidative/Nitrosative Stress and Immuno-inflammatory Pathways in Depression: Treatment Implications
Anderson, G., & Maes, M. H. J. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113196660738 · Cited by 147 · see citing works
Yan, D., Liu, X., & Guo, S.-W. (2019) · Scientific Reports · doi:10.1038/s41598-019-39170-w · Cited by 82 · see citing works
Antimicrobial Properties of Capsaicin: Available Data and Future Research Perspectives
Periferakis, A.-T., Periferakis, A., Periferakis, K., Căruntu, A., Bădărău, I. A., Săvulescu-Fiedler, I., Scheau, C., & Căruntu, C. (2023) · Nutrients · doi:10.3390/nu15194097 · Cited by 89 · see citing works
Bera, M. M., Lu, B., Martin, T. R., Cui, S., Rhein, L. M., Gerard, C. J., & Gerard, N. P. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101789 · Cited by 60 · see citing works
Zhou, Y., Zhao, L., Xiong, T., Chen, X., Zhang, Y., Yu, M., Yang, J., & Yao, Z. (2013) · Breast Cancer Research and Treatment · doi:10.1007/s10549-013-2599-6 · Cited by 49 · see citing works
Regulation of Carcinogenesis by Sensory Neurons and Neuromediators
Erin, N., Shurin, G. V., Baraldi, J. H., & Shurin, M. R. (2022) · Cancers · doi:10.3390/cancers14092333 · Cited by 48 · see citing works
Sumpter, T. L., Ho, C. H., Pleet, A. R., Tkacheva, O. A., Shufesky, W. J., Rojas‐Canales, D. M., Morelli, A. E., & Larregina, A. T. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.07.036 · Cited by 47 · see citing works
Truncation of neurokinin-1 receptor—Negative regulation of substance P signaling
Spitsin, S. V., Pappa, V., & Douglas, S. D. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mir0817-348r · Cited by 44 · see citing works
Self-citationInteraction between nectin-1 and the human natural killer cell receptor CD96
Holmes, V. M., de Motes, C. M., Richards, P. T., Roldan, J., Bhargava, A. K., Orange, J. S., & Krummenacher, C. (2019) · PLoS ONE · doi:10.1371/journal.pone.0212443 · Cited by 43 · see citing works
Self-citationThe neuropeptide galanin modulates natural killer cell function
Koller, A., Bianchini, R., Schlager, S., Münz, C., Kofler, B., & Wiesmayr, S. (2016) · Neuropeptides · doi:10.1016/j.npep.2016.11.002 · Cited by 42 · see citing works
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Tebas, P., Spitsin, S. V., Barrett, J. S., Tuluc, F., Elci, O. U., Korelitz, J., Wagner, W., Winters, A., Kim, D., Catalano, R., et al. (2015) · AIDS · doi:10.1097/qad.0000000000000638 · Cited by 40 · see citing works
Self-citationThe Effect of Aging on Nerve Morphology and Substance P Expression in Mouse and Human Corneas
Barbariga, M., Rabiolo, A., Fonteyne, P., Bignami, F., Rama, P., & Ferrari, G. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.18-24707 · Cited by 36 · see citing works
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Mishra, A., & Lal, G. (2021) · Current Research in Immunology · doi:10.1016/j.crimmu.2021.06.001 · Cited by 35 · see citing works
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Nizam, E., Köksoy, S., & Erin, N. (2020) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02574-z · Cited by 30 · see citing works
CD2 Promotes Human Natural Killer Cell Membrane Nanotube Formation
Comerci, C. J., Mace, E. M., Banerjee, P. P., & Orange, J. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047664 · Cited by 27 · see citing works
Self-citationTebas, P., Tuluc, F., Barrett, J. S., Wagner, W., Kim, D., Zhao, H., Gonin, R., Korelitz, J., & Douglas, S. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024180 · Cited by 27 · see citing works
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Sipprell, S. E., & Marriott, I. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-22194-1.00019-7
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- Authors
- Monaco-Shawver, L., Schwartz, L., Tuluc, F., Guo, C.-J., Lai, J. P., Gunnam, S. M., Kilpatrick, L. E., Banerjee, P. P., Douglas, S. D., & Orange, J. S.
- Affiliations
- Children's Hospital of Philadelphia (US)
- The Children's Hospital of Philadelphia Research Institute, University of Pennsylvania, Pediatrics , Philadelphia, Pennsylvania, USA
- Corresponding author
- Kilpatrick, Laurie E
- Orange, Jordan S
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10-12
- Volume
- 89
- Issue
- 1
- Pages
- 113-125
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- PMC
- PMC3004520
- OpenAlex
- W2147941193
- Cited by
- 39
- References
- 74
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (P01 MH076388, R01 MH049981, U01 MH090325)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Keywords
- substance P, neurokinin-1 receptor, NK cell cytotoxicity, NK cell degranulation, neuroimmunomodulation, intracellular calcium signaling, ERK1/2 phosphorylation, NF-κB activation, natural cytotoxicity receptors, depression, HIV infection
- MeSH terms
- Cell Line, Cytotoxicity, Immunologic, Enzyme Activation, Gene Expression Regulation, Humans, Interferon-gamma, Killer Cells, Natural, Kinetics, Phosphorylation, Protein Binding, RNA, Messenger, Substance P, Cell Degranulation, NF-kappa B, Receptors, Neurokinin-1, Calcium Signaling, Intracellular Space, Extracellular Signal-Regulated MAP Kinases, Granzymes
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