C3d-K, a kallikrein cleavage fragment of iC3b is a potent inhibitor of cellular proliferation.
The C3d-K fragment generated from human iC3b by plasma kallikrein is a potent suppressant of cellular proliferation. Originally characterized as inhibiting human and murine T lymphocyte function, C3d-K is shown in these studies to suppress mitogen-induced B cell growth, the spontaneous proliferation of several tumor cell lines, as well as all forms of T cell proliferation, including that induced by interleukin 2 (IL 2). In addition, synthesis of IL 2 in mixed lymphocyte cultures is blocked by C3d-K, but not IL 2 synthesis induced by Con A. The C3d-K fragment has no effect on resting cells; however, sensitivity to the inhibitory effect of C3d-K is acquired during the activation process. Because the proliferation of mitogen-activated spleen cells is not inhibited by exposure to C3d-K for the initial 24 hr of culture, only late steps in the cell activation process are C3d-K sensitive. When C3d-K is present throughout the course of the 72-hr culture, suppression was observed. Data obtained with the tumor cell lines suggest that once suppression is achieved, it is long-lasting even in the absence of C3d-K.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003176:Complement C3 / Q000378:metabolism / Q000502:physiology*; D003179:Complement C3b / Q000378:metabolism*; D015933:Complement C3d; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D007610:Kallikreins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
D003176:Complement C3; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D003208:Concanavalin A; D003179:Complement C3b; D015933:Complement C3d; D007610:Kallikreins