The MBL‐complex is necessary for FeCl3‐mediated thrombosis

Abstract

Occlusive thrombosis, resulting from atherosclerotic plaque rupture or restenosis plays an important role in the onset of two major causes of death in developed nations: myocardial infarction and ischemic stroke. It is well‐known that the complement and coagulation systems interact, however no studies have investigated the specific role of the lectin complement pathway in thrombus formation. Thus, the purpose of this study was to examine the role of the complement system, specifically the mannose‐binding lectin (MBL) complex, in a mouse model of ferric‐chloride (FeCl3)‐induced thrombosis. For this model, 2 strips of Whatman paper were soaked in 3.5% FeCl3 and applied to either side of the exposed right carotid artery for 3min then removed. Blood flow was measured at baseline, during FeCl3 administration, and for 30min following FeCl3 exposure using a Doppler flow probe positioned distal to the FeCl3 application. Using wild‐type (WT) and C2/fB−/− mice, we observed occlusive thrombosis of the carotid artery 10min after FeCl3 administration. In contrast, MBL−/− mice had significantly decreased FeCl3‐induced thrombosis formation compared to WT or C2/fB−/− mice (P<0.05). In conclusion, our study provides evidence for a significant role for the MBL‐complex in FeCl3‐induced coagulation and may lead to the development of improved anti‐thrombotic therapies. Supported by HL56086, HL92469 and HL99130.