The participation of leukocytes in coagulant reactions

Leukocytes play an important role not only in the physiological processes of inflammation and wound healing, but also in the pathophysiological process of atherosclerosis. Integral to their role in these processes is the ability of these cells to participate in and regulate the molecular events leading to thrombin formation, which is supported by several observations. For example, there is an active fibroproliferative response [1] as well as fibrin deposition [2,3] accompanying these processes. Furthermore, monocytes interact with vascular endothelium, platelets, and mesenchymal cells, all of which respond to thrombin. Thrombin promotes numerous cellular effects including chemotaxis, proliferation, cytokine release, and extracellular matrix turnover [4]. Thus, it is likely that thrombin production at the leukocyte surface provides this important bioregulatory molecule at precise locations. Typically, thrombin formation requires a series of zymogen to protease conversions catalyzed by select enzymatic complexes assembled on appropriate cellular membrane surfaces. Leukocytes, in particular monocytes, possess a variety of mechanisms to efficiently initiate and amplify thrombin generation at their membrane surface. Monocytes/macrophages actively regulate both the assembly and function, as well as the substrate specificity, of various coagulation enzymes through a variety of mechanisms including: the expression of membrane binding sites (receptors) for the various protein constituents of the complexes; the expression of different receptors, which may alter the function of the protease; and the expression of membrane proteases, which may induce cofactor and/or protease function. Monocyte stimulation with various agonists modulates many of these responses as does their adherence to, and differentiation on, various substrates [5–11]. The role of monocytes/macrophages in tissue factor/factor VIIa-catalyzed initiation of blood coagulation