Suppression of phagocytosis by dexamethasone in macrophage cultures: inability of arachidonic acid, indomethacin, and nordihydroguaiaretic acid to reverse the inhibitory response mediated by a steroid-inducible factor.

Glucocorticoid steroids inhibit phagocytosis and cell spreading in cultures of murine resident peritoneal macrophages. It is postulated that these suppressive responses are mediated by a steroid-induced substance elaborated from dexamethasone-treated macrophages. Accordingly, dialyzed medium from dexamethasone-treated cultures was analyzed for the presence of a factor that inhibits phagocytosis and cell spreading in macrophage cultures not exposed to the steroid. When previously untreated macrophages were supplied dialysates from steroid-treated cultures, cell spreading and the phagocytic capacity (i.e. percentages of phagocytes in macrophage populations and the ability of phagocytes to ingest heat-killed Saccharomyces cerevisiae particles) decreased dramatically between 2 and 24 h after exposure. A lesser transient inhibitory response was observed when dialysates from untreated cultures were used. Relative to these controls after 48 h, phagocytic capacity and cell spreading remained suppressed in cultures treated with dialysates from dexamethasone-treated cultures. The addition of arachidonate, in the absence and presence of cyclooxygenase and lipoxygenase inhibitors, did not affect the phagocytic capacity of control macrophages. Furthermore, the addition of these compounds, either alone or in combination, to dexamethasone-treated cultures did not modulate the steroid-induced suppression of phagocytosis. These results support the hypothesis that the inhibition of phagocytosis and cell spreading may be mediated by a dexamethasone-induced non-dialyzable factor. In addition, the inability of arachidonic acid and inhibitors of prostaglandin and leukotriene biosynthesis to reverse the steroid-induced suppression of phagocytosis implies that the inhibition of this important macrophage function is not associated with the failure of dexamethasone-treated macrophages to release these mediators.