Temporal down-regulation of Fc gamma RIII expression and Fc gamma receptor-mediated phagocytosis in human monocyte-derived macrophages induced by TNF-alpha and IL-1 beta.

Effects of tumor necrosis factor (TNF-alpha) and interleukin-1 beta (IL-1 beta) on the expression of Fc gamma receptors (Fc gamma Rs) and on Fc gamma R-mediated phagocytosis in human monocyte-derived macrophages (MDMs) have been determined. Treatment of MDMs with TNF-alpha (400 pg/ml) or IL-1 beta (400 pg/ml) for 80 min decreased cell surface Fc gamma RIII expression, as measured by flow cytometry (FACS), while the levels of surface Fc gamma RI and Fc gamma RII remained unchanged. Surface Fc gamma RIII expression remained depressed for 7 h after exposure of MDMs to either cytokine but then rose progressively until, by 24 h of stimulation, the levels were at least as high as those on unstimulated cells. In parallel with cell surface Fc gamma RIII levels, phagocytosis of immunoglobulin G-opsonized fluorescent beads, as measured by FACS, decreased and then increased over time after stimulation of MDMs with TNF-alpha while the opsonin-independent phagocytic activity was unchanged, suggesting that among the three classes of Fc gamma receptors on macrophages, Fc gamma RIII may play a critical role in regulating opsonic phagocytosis. After treatment with IL-1 beta, both opsonic and nonopsonic phagocytic activities of MDMs were significantly decreased, regardless of Fc gamma RIII levels. FACS analysis of rhodamine-phalloidin-stained MDMs showed that after incubation with IL-1 beta, but not TNF-alpha, the content of F-actin declined in MDMs, coinciding with inhibition of particle phagocytosis. Rapid down-regulation and subsequent recovery of macrophage Fc gamma RIII expression following cytokine stimulation could serve as a novel regulatory mechanism employed by inflammatory cells in host defense.