Macrophage activation for tumor cytotoxicity: regulatory mechanisms for induction and control of cytotoxic activity.

Macrophage activation for nonspecific tumor cytotoxicity occurs after completion of a series of reactions, each of which requires the simultaneous presence of effective activation signals and competent mononuclear phagocytes. This reaction sequence can be conceptually divided into three phases: precursor differentiation, priming, and trigger reactions, The first phase involves recruitment and differentiation of immature, blood-derived mononuclear phagocytes into competent, lymphokine-responsive cells by factors generated at the site of inflammation. Complete expression of nonspecific effector function by activated macrophages occurs after two additional phases: inflammatory macrophages first respond to certain lymphokine signals and enter into a receptive or primed state in which they are not yet cytotoxic, but can then respond or be triggered by other signals to develop full functional activity. These lymphokine-priming and trigger signals form the basis of a regulatory system that sets the threshold and determines the onset of macrophage effector activity.