Activation of macrophages to kill rickettsiae and Leishmania: dissociation of intracellular microbicidal activities and extracellular destruction of neoplastic and helminth targets.

Mononuclear phagocytes undergo dramatic changes during differentiation from bone marrow stem cells to resident tissue macrophages. Throughout differentiation, cells lose or acquire numerous morphologic, metabolic and functional capacities such that mature, resident macrophages of one tissue often bear little resemblance to resident cells of another. Superimposed on the intrinsic continuum of mononuclear phagocyte differentiation are the reactive changes in macrophages induced by endogenous and exogenous stimuli: the ability of mononuclear phagocytes to respond to a particular stimulus may also change with cell differentiation. This dynamic interaction of cell differentiation and response to a micro-environment, and the resulting heterogeneity among mononuclear phagocytes for many functional characteristics, is clearly illustrated by the effector activities of activated macrophages that we describe in this report. Despite the common regulatory events for induction and expression of transient nonspecific cytotoxic reactions effective against such diverse targets as rickettsiae, leishmania, schistosomula, and neoplastic cells, these effector functions can be dissociated by the cells that perform the effector activity, and the signals that regulate these activities. The differential susceptibility of the various targets to particular killing mechanisms induced by LK in responsive populations only adds to the complexity of these in vitro analyses. The details of effector functions of activated macrophages are unique for each target.