Soluble mediators of injury of the microvasculature; Hageman factor and the kinin forming, intrinsic clotting and the fibrinolytic systems

Studies on Hageman factor have revealed that this protein of approximately 80,000 MW is activated in both solid and fluid phase. In solid phase, the molecule interacts with negatively charged particles without undergoing cleavage. Enzymatic activity is acquired, presumably following a conformational change in the structure of Hageman factor. In fluid phase, the enzymes kallikrein, plasmin, and plasma thromboplastin antecedent (clotting Factor XI) all activated Hageman factor, and in human plasma, the Hageman factor is readily cleaved during this activation. Evidence is presented indicating that kallikrein is the most important fluid phase activator and that the activation with kallikrein is essential for the normal function of the intrinsic clotting, fibrinolytic and kinin forming systems. Information on the role of these systems in immunopathology awaits careful analyses of the function of individual components and means of their accurate detection and quantitation.