C3d-K, a kallikrein cleavage fragment of iC3b is a potent inhibitor of cellular proliferation.

Abstract

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.