Non-immunological recognition and killing of xenogeneic cells by macrophages. II. Mechanism of killing.

Macrophages are cytotoxic to chicken embryonic fibroblasts without either previous activation or lymphocyte assistance. This cytotoxic activity (xenolysis) is expressed by non-activated macrophages from athymic mice as well as by pure macrophage populations. Neither macrophage lysate nor supernatants of macrophages cultivated with fibroblasts cause xenolysis. Unlike macrophage tumoricidal activity, killing of xenogeneic cells is not dependent on specific serum factors and is expressed by macrophages from a lipopolysaccharide (LPS) unresponsive strain (C3H/HeJ). Xenolysis is expressed also by trypsin-treated macrophages and by macrophages from 5-day-old cultures. Killing of chicken fibroblasts by macrophages is not affected by hydrocortisone (100 micrograms/ml) gold salt (1 mg/ml) and colchicine (100 micrograms/ml). On the other hand, cytochalasin B (10 micrograms/ml) completely abolishes the killing, probably by interfering with macrophage mobility and extension of filopodia toward the targets. It is suggested that the xenolytic activity of macrophages represents a primitive trait of phagocytes which assists the body in defence against multicellular parasites.