Development of antitumor activity in LPS-stimulated mouse granuloma macrophages. Regulation by eicosanoids

Macrophage-mediated antitumor activity is believed to be regulated by E-type prostaglandins released by target cells or even by macrophages themselves. In these studies we showed that a subcutaneous injection of polyacrylamide beads (Biogel P100), induced in mice, a population of immature macrophages which became fully cytostatic to syngeneic P815 mastocytoma when pulsed in vitro with lipopolysaccharide (LPS). Blockade of prostaglandin synthesis by indomethacin prevented LPS effect and led to a substantial resumption of target growth. Addition of PGE2 did not reverse the indomethacin effect but inhibited macrophage-mediated cytostatic activity. These findings suggest that acquisition of cytostatic properties by macrophages is, at a certain stage of their maturation, under the control of both PGE2 and another endogenously produced eicosanoid.