Synergistic effect between neutrophils and Corynebacterium parvum in the process of macrophage activation.

Adoptive transfer of granulocytes exposed to Corynebacterium parvum in vivo or in vitro efficiently activates murine peritoneal macrophages in vivo. A comparison of the amount of bacteria required to produce similar levels of cytolytic activity indicated that 2 X 10(7) intracellular (neutrophil) bacteria were as efficient as 1 X 10(10) bacteria introduced directly. The time courses of macrophage cytotoxicity induced by these two methods were found comparable. Similar levels of activity were also observed in tumor cytostasis and inhibition of phytohemagglutinin-induced mitogenesis assays. However, when spleen size or cell division in the spleen or bone marrow was assessed, differences were found. Direct C. parvum injection caused marked splenomegaly. The proliferative fraction of cells in the spleen and bone marrow was significantly increased over both control and C. parvum-induced neutrophil groups. These results further document the nature and efficiency of the interaction between neutrophils and bacteria in macrophage activity. The findings are significant in that they demonstrate a novel way to activate macrophages in vivo without causing the potentially harmful side effects which result from direct injection of the biological response modifier.