Original basic research

Enhancement of fibrinogen-triggered pro-coagulant activation of monocytes in vitro by matrix metalloproteinase-9

Nicole C Kaneider¹ , Birgit Mosheimer¹ , Andrea Günther² , Clemens Feistritzer¹ and Christian J Wiedermann³

¹  Division of Internal Medicine I, Department of Internal Medicine, Medical University of Innsbruck, Peter-Anich-Street 35, 6020 Innsbruck, Austria

²  Division of Vascular Surgery, Department of Surgery, Medical University of Innsbruck, Peter-Anich-Street 35, 6020 Innsbruck, Austria

³  Department of Internal Medicine, Central Hospital of Bolzano, Lorenz-Böhler-Street 5, 39100 Bolzano (BZ), Italy

author email corresponding author email

Thrombosis Journal 2010, 8:2doi:10.1186/1477-9560-8-2

Published:	29 January 2010

Abstract

Background

Interaction of fibrinogen with specific leukocyte integrins of monocytes may link coagulation and inflammation, however, the precise mechanism of fibrinogen leading to the pro-inflammatory and pro-coagulatory response on monocytes is yet unknown.

Results

Fibrinogen and its digestion fragment D induced pro-coagulant activation of monocytes as assessed in a cellular coagulation assay by reductions in clotting times. Pro-coagulant activation was reversed by blocking antibodies against Mac-1 or LFA-1. Pre-exposure of monocytes to the p38 MAPK inhibitor SB 202190 and the MEK1.2 inhibitor U0126 led to significant increasees in coagulation times whereas blocking JNKII with its inhibitor had no such effect. Blocking NFκB with MG-132 also inhibited pro-coagulant activation of monocytes by fibrinogen. A selective inhibitor of matrix metalloproteinase-9 increased times to clot formation whereas other matrix metalloproteinase inhibitors did not significantly interfere with fibrinogen-augmented clot formation in this assay. Treatment of monocytes with fibrinogen increased concentrations of matrix metalloproteinase-9 immunoreactivity in their supernatants.

Conclusions

Fibrinogen induces monocyte pro-coagulant activation in an integrin-, nuclear factor κB-, p38 MAPK-, and MEK1.2-dependent manner. Activation of monocytes by fibrinogen increases metalloproteinase-9 secretion, metalloproteinase-9 itself enhances monocyte coagulation by an autocrine mechanism. Results provide further evidence that mediators of hemostasis have a profound impact on cells of the immune system and are closely related to inflammatory pathways.