| Responses of neutrophils to anti-integrin antibodies depends on costimulation through low affinity Fc gamma Rs: full activation requires both integrin and nonintegrin signals. | |
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MedLine Citation:
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PMID: 15265942 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The relative contribution of integrin and nonintegrin signals to neutrophil activation is incompletely understood. Immobilized anti-integrin Abs were previously shown to induce robust activation of neutrophils without any additional stimulus, suggesting that cross-linking of integrins is sufficient for full activation of the cells. However, the possible contribution from other receptors has not been tested in this system. In this study, we show that neutrophil responses to anti-integrin Abs requires costimulation through low-affinity Fc gamma Rs. Murine neutrophils lacking the FcR gamma-chain or Fc gamma RIII failed to respond to immobilized Abs against beta(1), beta(2), or beta(3) integrins and the activation of wild-type cells could be prevented by blocking Abs against Fc gamma RII/III. Plate-bound anti-CD18 Abs initiated a respiratory burst from human neutrophils, but this response was abrogated when the F(ab')(2) of the same Abs were used or the cells were preincubated with Fc gamma RIIA-blocking Abs. Lack of Fc gamma RIII or administration of Fc gamma R-blocking Abs had no effect on responses of TNF-stimulated cells plated on fibrinogen or rICAM-1. TNF restored the respiratory burst of Fc gamma RIII-deficient neutrophils plated on anti-CD18 mAbs. The p38 MAPK inhibitor SB203580 attenuated the responses of neutrophils to anti-CD18 mAbs or TNF stimulation on a fibrinogen surface. Taken together, these results indicate that activation of low-affinity Fc gamma Rs is required for neutrophil responses induced by anti-integrin Abs and suggest that a second coactivation signal (e.g., through TNF or FcR ligation) is indispensable for full integrin-mediated activation of neutrophils. These second signals are interchangeable and they may converge on the p38 MAPK. |
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Authors:
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Zoltán Jakus; Giorgio Berton; Erzsébet Ligeti; Clifford A Lowell; Attila Mócsai |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 173 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-07-21 Completed Date: 2004-11-02 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 2068-77 Citation Subset: AIM; IM |
Affiliation:
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Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / pharmacology* Cell Adhesion / drug effects, physiology Enzyme Inhibitors / pharmacology Fibrinogen / metabolism Imidazoles / pharmacology Integrin beta Chains / immunology, physiology* Intercellular Adhesion Molecule-1 / genetics, metabolism MAP Kinase Signaling System / drug effects, physiology Mice Mice, Inbred C57BL Mice, Knockout Mitogen-Activated Protein Kinases / antagonists & inhibitors, physiology Neutrophils / drug effects* Phosphorylation Protein Processing, Post-Translational / drug effects Pyridines / pharmacology Receptor Aggregation Receptors, IgG / deficiency, drug effects, genetics, immunology, physiology* Recombinant Proteins / metabolism Respiratory Burst / drug effects Signal Transduction / physiology* Superoxides / metabolism p38 Mitogen-Activated Protein Kinases |
| Grant Support | |
ID/Acronym/Agency:
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DK58066/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Enzyme Inhibitors; 0/Fcgr1 protein, mouse; 0/Fcgr2b protein, mouse; 0/Fcgr3 protein, mouse; 0/Imidazoles; 0/Integrin beta Chains; 0/Pyridines; 0/Receptors, IgG; 0/Recombinant Proteins; 0/SB 203580; 11062-77-4/Superoxides; 126547-89-5/Intercellular Adhesion Molecule-1; 9001-32-5/Fibrinogen; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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