Sequential activation of murine mononuclear phagocytes for tumor cytolysis: differential expression of markers by macrophages in the several stages of development

Abstract

Murine mononuclear phagocytes in various stages of activation were elicited in vivo or induced in vitro. The cytolytic competence of each type of macrophage, before and after treatment with traces of endotoxin, was quantified. Populations of responsive, primed, and activated macrophages, but not resident macrophages, expressed five markers that have been reported to characterize inflammatory macrophages: increased spreading, increased phagocytosis via Fc and C3 receptors, increased secretion of plasminogen activator, and decreased content of the ectoenzyme 5' nucleotidase. Primed macrophages secreted cytolytic protease (CP) when pulsed with traces of endotoxin; the resident and responsive macrophages did not. The primed macrophages bound tumor cells to a considerable degree; the resident and responsive macrophages did not. The cytolytically activated macrophages bound tumor cells well and secreted lytic protease spontaneously. The capacity for augmented, selective binding of tumor cells is apparently induced in only one step by application of lymphokine(s). The capacity for secreting CP, however, is regulated in two steps; initial priming signals--lymphokine(s)--prepare the macrophages for secretion, and a second signal, such as endotoxin or endotoxin plus tumor cells, triggers the actual release of CP.