| Complement alternative pathway acts as a positive feedback amplification of neutrophil activation. | |
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MedLine Citation:
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PMID: 21063021 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Complement alternative pathway plays an important, but not clearly understood, role in neutrophil-mediated diseases. We here show that neutrophils themselves activate complement when stimulated by cytokines or coagulation-derived factors. In whole blood, tumor necrosis factor/formyl-methionyl-leucyl-phenylalanine or phorbol myristate acetate resulted in C3 fragments binding on neutrophils and monocytes, but not on T cells. Neutrophils, stimulated by tumor necrosis factor, triggered the alternative pathway on their surface in normal and C2-depleted, but not in factor B-depleted serum and on incubation with purified C3, factors B and D. This occurred independently of neutrophil proteases, oxidants, or apoptosis. Neutrophil-secreted properdin was detected on the cell surface and could focus "in situ" the alternative pathway activation. Importantly, complement, in turn, led to further activation of neutrophils, with enhanced CD11b expression and oxidative burst. Complement-induced neutrophil activation involved mostly C5a and possibly C5b-9 complexes, detected on tumor necrosis factor- and serum-activated neutrophils. In conclusion, neutrophil stimulation by cytokines results in an unusual activation of autologous complement by healthy cells. This triggers a new amplification loop in physiologic innate immunity: Neutrophils activate the alternative complement pathway and release C5 fragments, which further amplify neutrophil proinflammatory responses. This mechanism, possibly required for effective host defense, may be relevant to complement involvement in neutrophil-mediated diseases. |
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Authors:
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Laurent Camous; Lubka Roumenina; Sylvain Bigot; Soumeya Brachemi; Véronique Frémeaux-Bacchi; Philippe Lesavre; Lise Halbwachs-Mecarelli |
Publication Detail:
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Type: Journal Article Date: 2010-11-09 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 1340-9 Citation Subset: AIM; IM |
Affiliation:
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Inserm U 845, Université René Descartes, Hôpital Necker, Paris, France; and. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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