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Granzyme B: a new crossroad of complement and apoptosis.

Abstract

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+Show Affiliations

    ,

    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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    MeSH

    Apoptosis
    Complement System Proteins
    Granzymes
    Humans
    Multiple Trauma
    Signal Transduction

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    21948366