Macrophage-mediated tumor cell killing: lack of dependence on the cyclooxygenase pathway of prostaglandin synthesis.
M phi obtained directly from disaggregated murine Moloney sarcomas produced PGE2 and a hydroxy fatty acid derivative as the major products of arachidonic acid metabolism. M phi-immunoreactive PGE synthetic rates decreased substantially and cytotoxic activity was lost when freshly explanted tumor M phi were held in culture 24 hr. Such cultured M phi remained in a partially activated "primed" state, however, wherein the addition of minute (ng) amounts of bacterial lipopolysaccharide (LPS) returned cytolytic activity and PGE synthesis to original levels. Indomethacin-induced blockade of the M phi cyclooxygenase pathway inhibited PG synthesis by LPS-stimulated, primed M phi without affecting the return of cytolytic activity. We conclude, therefore, that the production of PG had no direct role in the mediation of tumor cell killing by activated M phi isolated from these neoplasms.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D007942:Leukemia, Experimental / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008979:Moloney murine leukemia virus / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis
D001095:Arachidonic Acids; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases