Lymphokine maintains macrophage activation for tumor cell killing by interfering with the negative regulatory effect of prostaglandin E2.
Mouse resident peritoneal macrophages activated with bacterial lipopolysaccharide (LPS) rapidly lost their ability to kill tumor cells in vitro. Such loss of killing has previously been attributed to the effects of prostaglandin E (PGE) produced by the LPS-stimulated macrophages. Macrophages exposed in the current study to both LPS and partially purified lymphokine did not lose cytolytic activity, in spite of the fact that these cells produced undiminished amounts of PGE, compared to controls. Cytolytic activity was shown to be retained under these conditions because lymphokine decreased the sensitivity of activated macrophages to the negative regulatory effects of PGE. The mechanism responsible for the lymphokine effect is not known; however, generalized inhibition of macrophage responsiveness to the hormone does not appear to be involved because lymphokine did not reduce the cyclic AMP response of macrophages, measured on a whole cell basis, after they were exposed to PGE.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D008222:Lymphokines / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D011458:Prostaglandins E / Q000096:biosynthesis / Q000494:pharmacology
D008222:Lymphokines; D011458:Prostaglandins E; D000242:Cyclic AMP