Fragment E derived from both fibrin and fibrinogen stimulates interleukin-6 production in rat peritoneal macrophages

Fibrin derived from fibrinogen after thrombin cleavage plays an essential r ole in forming blood clots. Fibrin as well as fibrinogen is also involved i n the induction of platelet aggregation, leukocyte cell adhesion and phagoc ytosis. An additional biological role of fibrin and fibrinogen is presented in this study. One of the proteolytic peptides of fibrin/fibrinogen, fragm ent E, and not fragment D, was able to stimulate rat peritoneal macrophages to express interleukin-6 (IL-6). The stimulation of fibrin/fibrinogen frag ment E on macrophages appeared to work in a dose- and time-dependent manner . Adherent fibrin fragment E was able to stimulate IL-6 expression as well as IL-6 protein production. The effect of fibrin fragment E was inhibited b y the addition of an excess amount of GPRP tetrapeptide, but not by GHRP, w hich are the amino acids derived from the amino terminus of fibrin alpha an d beta chains, respectively. These results suggest that fibrin as well as f ibrinogen function as a stimulator to macrophages, and leukocyte integrin p 150,95 (CD11c/CD18), not Mac-I (CD11b/CD18), is involved in mediating fibri n stimulatory activity in macrophages.