Platelets promote coagulation factor XII-mediated proteolytic cascade systems in plasma.
Blood coagulation factor XII (FXII, Hageman factor) is a plasma serine protease which is autoactivated following contact with negatively charged surfaces in a reaction involving plasma kallikrein and high-molecular-weight kininogen (contact phase activation). Active FXII has the ability to initiate blood clotting via the intrinsic pathway of coagulation and inflammatory reactions via the kallikrein-kinin system. Here we have determined FXII-mediated bradykinin formation and clotting in plasma. Western blotting analysis with specific antibodies against various parts of the contact factors revealed that limited activation of FXII is sufficient to promote plasma kallikrein activation, resulting in the conversion of high-molecular-weight kininogen and bradykinin generation. The presence of platelets significantly promoted FXII-initiated bradykinin formation. Similarly, in vitro clotting assays revealed that platelets critically promoted FXII-driven thrombin and fibrin formation. In summary, our data suggest that FXII-initiated protease cascades may proceed on platelet surfaces, with implications for inflammation and clotting.
1. Institute of Clinical Biochemistry and Pathobiochemistry, Josef-Schneider-Strasse 2, University of Würzburg, D-97080 Würzburg, Germany.
Julia
J
Johne
Constanze
C
Blume
Peter M
PM
Benz
Miroslava
M
Pozgajová
Melanie
M
Ullrich
Kai
K
Schuh
Bernhard
B
Nieswandt
Ulrich
U
Walter
Thomas
T
Renné
D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology*; D001920:Bradykinin / Q000096:biosynthesis; D005174:Factor XII / Q000502:physiology*; D006801:Humans; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007704:Kininogens / Q000096:biosynthesis; D008970:Molecular Weight; D012016:Reference Values; D013917:Thrombin / Q000096:biosynthesis; D013997:Time Factors
D007704:Kininogens; D005174:Factor XII; D013917:Thrombin; D001920:Bradykinin