Macrophage-Mediated Tumor Cell Killing: Lack of Dependence on the Cyclooxygenase Pathway of Prostaglandin Synthesis

Abstract

Mφ obtained directly from disaggregated murine Moloney sarcomas produced PGE₂ and a hydroxy fatty acid derivative as the major products of arachidonic acid metabolism. Mφ-immunoreactive PGE synthetic rates decreased substantially and cytotoxic activity was lost when freshly explanted tumor Mφ were held in culture 24 hr. Such cultured Mφ 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 Mφ cyclooxygenase pathway inhibited PG synthesis by LPS-stimulated, primed Mφ 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 Mφ isolated from these neoplasms.