ИСТИНА

The intrinsic pathway of blood plasma coagulation initiates after a contact with some foreign surface by activation of the coagulation contact pathway comprising proteolytic cleavages of plasma proteins factor XII (FXII) and prekallikrein (PKr) promoted by the surface and requiring a cofactor, high molecular weight kininogen (HMWK). Animal studies suggest a potential pivotal role of contact pathway for thrombosis while it is dispensable in normal hemostasis. Yet, physiological activation mechanisms of FXII remain unclear [1]. One of the frequently occurring events of contact pathway activation is bacterial infection. The FXII and PK seem to be activated by components of the outer leaflet of gram-negative bacteria outer membrane, lipopolysaccharides (LPS) or endotoxins [2]. In vitro contact pathway activation by LPS assessed by kallikrein activity has an optimum around concentrations of LPS equaling 100 μg/ml suggesting surface-dependent mechanisms of contact pathway activation by endotoxins. [3,4]. Aims: Experimental investigation and computational analysis of the molecular mechanisms governing contact pathway activation on the bacterial endotoxins.