Abnormal platelet function in C3-deficient mice

SUMMARY BACKGROUND AND OBJECTIVES: The complement system is a biochemical cascade composed of several plasma proteins that can interact with endothelial cells and blood cells, including platelets. In order to investigate the effect of the complement system on platelets, we studied platelet function in C3-deficient mice that lack complement activity.

Tail-cut bleeding time was prolonged and platelet aggregation in response to protease-activated receptor-4 (PAR4) peptide was decreased in C3-deficient mice as compared with wild-type littermates. Platelet aggregation in response to other agonists (ADP and collagen) was similar between C3-deficient mice and their normal littermates. Isolated platelets from wild-type mice aggregate less in C3-deficient plasma than in normal plasma, and, conversely, addition of plasma from wild-type mice or plasma-purified C3 improved aggregation of C3-deficient platelets. We also monitored the formation of murine arteriole or venule thrombi in an intravital microscopy thrombosis model. We found that C3-deficient mice had a significantly delayed thrombotic response in arterioles as compared with their wild-type littermates. Furthermore, thrombi in C3-deficient mice were less stable and embolized more frequently than those in wild-type mice.

Platelets of C3-deficient mice have subnormal function, resulting in a prolonged tail-cut bleeding time and delayed thrombosis after vessel wall injury.