Macrophage Fcγ2b receptor expression and receptor- mediated phospholipase activity: regulation by endogenous eicosanoids

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Abstract
The expression of Fcγ2b receptors and receptor-mediated arachidonic acid metabolism by murine peritoneal macrophages was examined in vitro. The expression of Fcγ2b receptors was found to increase progressively with time in culture and this increase was dependent on protein synthesis and glycosylation. The increase in Fcγ2b receptor expression was inhibited by hydrocortisone and by BW755C, an inhibitor of both the lipoxygenase and cyclo-oxygenase pathways of arachidonic acid metabolism. Inhibition by BW755C was found to be reversed in the presence of exogenous leukotriene D4. In contrast, selective inhibition of the cyclo-oxygenase pathway by indomethacin enhanced the increase in receptor expression. This enhancement was only partially reversed by exogenous prostaglandin (PG)E2. Interaction of the FCγ2b receptor with ligand in the form of erythrocytes specifically sensitized with IgGzb resulted in the release and subsequent metabolism of arachidonic acid. PGE2 was found to be the principal product. Occupation of the Fcγ2a receptor did not result in arachidonic acid release. Down regulation of Fcγ2b receptor expression produced a commensurate reduction in receptor-mediated phospholipase activity measured by arachidonic acid release. Macrophages cultured for 24 h in the presence of fetal calf serum without additional stimuli produced substantial amounts of eicosanoids. PGI2 was the principal product. Taken together these data demonstrate a potential feedback regulation of receptor-triggered arachidonic acid metabolism by eicosanoids acting at the level of Fcγ2b receptor expression.