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.