| Granzyme B: a new crossroad of complement and apoptosis. | |
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MedLine Citation:
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PMID: 21948366 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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In response to severe tissue trauma, several "molecular danger" sensing and signaling pathways are activated, especially the complement and the apoptosis cascade. Although possible crossroads between both systems have been proposed, little is known about the underlying molecular interactions. In this study a new interaction interface is presented for C3a and C5a generation by the pro-apoptotic factor granzyme B. In vitro incubation of the central human complement components C3 and C5 with the serine protease granzyme B resulted in a concentration-dependent production of the anaphylatoxins C3a and C5a. The so generated anaphylatoxin C5a was chemotactic active for isolated human neutrophils. In a translational approach, intracellular granzyme B concentration in leukocytes was determined early after severe tissue trauma. In comparison to healthy volunteers, multiple injured patients (less than one hour after trauma, Injury Severity Score > 18, n = 5) presented a significant increase in granzmye B levels in neutrophils and lymphocytes. Thus, tissue trauma is associated with early activation of both, the complement and apoptosis system. The present data suggest a new form of interaction between the complement and the apoptosis system on the level of granzyme B that is capable to generate C3a and C5a independently of the established complement proteases. |
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Authors:
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Mario Perl; Stephanie Denk; Miriam Kalbitz; Markus Huber-Lang |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Advances in experimental medicine and biology Volume: 946 ISSN: 0065-2598 ISO Abbreviation: Adv. Exp. Med. Biol. Publication Date: 2012 |
Date Detail:
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Created Date: 2011-09-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0121103 Medline TA: Adv Exp Med Biol Country: United States |
Other Details:
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Languages: eng Pagination: 135-46 Citation Subset: IM |
Affiliation:
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Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, University Hospital of Ulm, Steinhoevelstr. 9, 89075, Ulm, Germany, mario.perl@uniklinik-ulm.de. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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