Cytolytic heterogeneity of polymorphonuclear leukocytes in killing of murine tumor cells.

Murine inflammatory polymorphonuclear leukocytes (PMN) and inflammatory ascitic fluid were found to contain cytotoxin. This cytotoxin was not oxygen metabolites, but a protein with a molecular weight of 70 kilodaltons as determined by high-performance liquid chromatography. However, the cytolytic activity was completely neutralized by anti-murine tumor necrosis factor (TNF) antibody, suggesting that PMN cytotoxin is a TNF-like molecule or TNF itself. Cytolytic heterogeneity of PMN was also demonstrated: immature PMN obtained from ascitic fluid 6 hr after caseinate injection showed stronger cytotoxicity than mature PMN obtained 3 hr after the injection. However, mature PMN (3 hr) contained more cytotoxin than immature PMN (6 hr). This discrepancy may be due to differences in the abilities of these PMN to synthesize and release cytotoxin. These results indicate that not only macrophages, but also inflammatory PMN can produce a TNF-like cytotoxin and that cytolytic heterogeneity of PMN exists in tumor killing.