Premium
Crosstalk of the Complement and Coagulation System
Author(s) -
Amara Umme,
Albers Sonja,
Gebhard Florian,
Bruckner Uwe B.,
HuberLang Markus
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.673.4
Subject(s) - thrombin , serine protease , proteases , chemistry , complement system , factor ixa , protease , biochemistry , coagulation , serine , enzyme , pharmacology , immunology , factor x , biology , platelet , immune system , medicine , psychiatry
The complement and coagulation systems are phylogenetically old and important ingredients of innate immune effectors that sense incoming signals of danger. The possible crosstalk and the precise pathways, by which the activation of coagulation triggers the complement cascade and vise versa, remain unclear. Therefore, in the current study the coagulation factors FXIa, FXa, FVIII, FVII, FVIIa, plasminogen, PC, aPC and thrombin were investigated for their potency to in vitro generate C3a and C5a. Material and Methods: In vitro cleavage experiments with incubation of native C3/C5 ± coagulation factors (FXa, FXIa, FIXa, thrombin) ± various serine protease inhibitors (aprotinin, leupeptine, pefabloc, protease inhibitor cocktail) were performed at 37°C dose‐ and time‐dependently by western blots. The enzymatic activity was assessed by ELISA (C3a Quidel REF A015; C5a, DRG Diagnostic REF EIA 3327). Results: This study demonstrates bi‐directional interaction of both cascades as the coagulation factors Xa, Xia, IXa and thrombin can dose‐ and time‐dependently cleave the key proteases of the complement system, C3 and C5, and generate biologically active C5a and C3a, resp, as detected by WB, ELISA and chemotactic activity assays of either HMC‐1 cells or neutrophils. The clotting factor FXIa, FXa, IXa and thrombin‐induced C3 and C5 cleavage activity could dose‐dependently be blocked by the serine protease inhibitor leupeptine and by the structure‐dependent inhibitor pefabloc. Furthermore, FXa exhibited maximal enzymatic activity of all measured coagulation factors (FXa