Mononuclear phagocytes constitute an important element of the host's defenses against the development and spread of neoplasia. When macrophages are activated for cytolysis, they effectively and selectively lyse tumor cells; but the precise mechanisms responsible for this target recognition and destruction remain to be defined in full. We have established that the activation of macrophages alters their function so that the macrophages selectively bind neoplastic targets and secrete a potent cytolytic neutral protease, secreted only by activated macrophages. Over the last 3 years we have defined three distinct forms of lysis: (1)\a direct antibody-independent lysis; (2)\a rapid antibody-dependent lysis; and (3)\a slow antibody-dependent lysis. We have found that each form of lysis requires two steps. Recognition and secretion of lytic mediators. All three forms of lysis, however, have different recognition and effector mechanisms and differ in macrophage activation. We are currently defining in molecular terms the capacities needed for each form of lysis. Exciting developments in these studies have been the development of evidence that a receptor is involved on the recognition in the antibody-independent lysis and the further progress toward purification of the novel lytic protease involved in this form of lysis. Studies over the coming year are aimed at understanding this form of lysis in molecular terms and studying the cell biology that leads to effective recognition. (MB)
NIH ExPorter
NIH ExPorter