Available evidence indicates that blood clotting contributes to tissue damage in a variety of inflammatory reactions, but mechanisms triggering the coagulation system in these reactions are poorly understood. In experiments with leukocytes isolated from canine kidney allograft recipients and from rabbits with Shwartzman reactions, we have recently found new evidence indicating that increases of leukocyte tissue factor (tissue thromboplastin) activity may be etiologic in thrombosis and fibrin deposition during allograft rejection as well as in disseminated intravascular coagulation due to endotoxemia. Experiments proposed here are designed to further investigate the possible thrombogenic role of procoagulant activity produced by leukocytes in inflammatory reactions including in vivo animal models of human disorders established in our laboratory during the present grant period, e.g., acute kidney allograft refection and Shwartzman reactions. Added to these models will be bacterial pneumonia and hemolytic transfusion reactions. In addition, we will further investigate a T-lymphocyte independent pathway of procoagulant activity generation recently elucidated in our laboratory. To gain a better understanding of the composition and distribution of tissue factor in inflammatory cells, biochemical characterization of leukocyte tissue factor will be carried out using clotting Factor VII the molecular substrate for time factor, anti-factor VII hybridoma antibodies as probes.
