TUMOR-NECROSIS-FACTOR PRODUCTION BY HUMAN GRANULOCYTES

Human polymorphonuclear leukocytes kill WEHI 164 cells in an 18-hour Cr-51 release assay. Antibody to human tumor necrosis factor (TNF) blocks the lysis of targets mediated by human granulocytes. Resting granulocytes produce an undetectable amount of TNF, if any. Granulocytes stimulated with Staphylococcus aureus release 250-500 U/ml TNF-alpha. The specificity of the released TNF in the WEHI 164 cytotoxicity assay was confirmed by using neutralizing anti-TNF-alpha monoclonal antibodies. The thymidine uptake of endothelial cells was inhibited by granulocyte-derived TNF. The identity of TNF-alpha was further confirmed by molecular weight determination, by gel filtration on Sephacryl S-200, with a result of approximately 44,000. Besides their antimicrobial capacity, therefore, granulocytes may contribute to tumor rejection, inflammation and septic infections by releasing TNF.