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Synergistic Effect between Neutrophils and Corynebacterium parvum in the Process of Macrophage Activation¹

Cancer Research Center [S. K. C., S. H.], Departments of Obstetrics and Gynecology [S. H.] and of Microbiology and Immunology [S. H.], University of North Carolina, Chapel Hill, North Carolina 27514

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 10⁷ intracellular (neutrophil) bacteria were as efficient as 1 x 10¹⁰ 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.

¹ This investigation was supported by National Cancer Institute Grant PO1-CA29589.

² Recipient of NIH National Service Award CA09156 from the National Cancer Institute. Present address: 508 Woodruff Memorial Research Building, Department of Microbiology and Immunology, Emory University, Atlanta, Ga. 30322.

³ To whom requests for reprints should be addressed.

Received 2/14/83. Accepted 9/14/83.