Factor XIII of blood coagulation inhibits the oxidative phagocyte metabolism and suppresses the immune response in vivo.

Factor XIII of blood coagulation (F XIII) belongs to the family of transglutaminases and is a major cell product of certain subsets of macrophages. The gene for F XIIIA is coupled to the immune response genes of the HLA-region on chromosome 6. F XIII dose- dependently inhibits the in vitro chemiluminescence response of human phagocytes. About 0.1 units of F XIII/ml (final) decreased the chemiluminescence response to about 50%. In addition, about 0.6 units of F XIII/ml inhibits 50% of the release of the lysosomal hydrolase N-acetyl-beta glucosaminidase in both immune complex stimulated and unstimulated monocytes. Intraperitoneal application of F XIII reduced the activity of phagocytes in a F XIII dose dependent manner. 0.25 units of F XIII reduced the chemiluminescence reaction of murine peritoneal M phi to about 50% of the activity of PBS treated animals after 2 or 24 hours of in vivo incubation. In the Fisher/Lewis rats skin transplantation model, injections of 5 units of F XIII/animal on days 1-7 or on days 10-17 increased the survival times of the transplants from the control value of 17.0 +/- 1.4 to 26.0 +/- 2.0 and 23.0 +/- 2.4 days, respectively. F XIII may represent a novel and physiological immune suppressive agent for a broad range of human diseases of autoimmune character.