JFRA-103 from the American Cancer Society, and a grant-in-aid from the American Heart Association with funds contributed in part by the Florida Affiliate. P. Detmers is an Arthritis

Receptors for C3 bind ligand and generate intracellular signals that lead to the engulfment of C3-coated particles. Recent experiments suggest that both the binding and the subsequent signal transduction activities of C3 receptors can be regulated. Cultured human monocytes (MO) 1 express receptors for C3b (CR1) and C3bi (CR3) that bind ligand-coated particles but do not signal the cell to initiate phagocytosis. After stimulation of the MO with PMA (1), or after interaction of the MO with surfaces coated with fibronectin (Fn, reference 2), CR1 and CR3 readily generate signals leading to phagocytosis. Thus PMA and Fn regulate the signaling capacity of CR1 and CR3 in these cells. In polymorphonuclear leukocytes, both the binding and the signaling activities are coordinately regulated. Brief (15 min) stimulation with PMA increases binding and signaling activities of CR 1 and CR3, but prolonged (60 min) incubation with PMA eliminates both binding and signaling (3). Since the PMA-mediated decline in the binding capacity of CR1 and CR3 is not accompanied by a loss of cell surface receptors, it appears that PMA regulates the binding and signaling activities o f existing cell surface receptors. In this report, we show that treatment of human monocytes and MO with recombinant IFN-~, causes CR1 and CR3 to lose the ability to bind ligand. IFN"),-treated cells express normal levels of cell surface CRI and CR3 as measured with anti-receptor antibodies, and the inhibition of ligand binding by CR 1 and CR3 is reversed in minutes by interaction of the phagocytes with Fn-coated surfaces. Therefore, cultivation with IFN-~, causes a reversible change in the nature of these receptors, which prevents them from interacting with ligand. Although Fn enables CR1 and CR3 on IFN-~'-treated MO to bind ligand, these receptors fail to promote phagocytosis (signaling). For signaling to occur, IFNy-treated cells require exposure to both Fn and PMA. PMA enables only signaling This work was supported by grants AI22003 and CA30198 from the United States Public Health Service, JFRA-103 from the American Cancer Society, and a grant-in-aid from the American Heart Association with funds contributed in part by the Florida Affiliate. P. Detmers is an Arthritis Foundation Investigator. Abbreviations used in this paper: Fn, fibronectin; HSA, human serum albumin; E, sheep erythrocyte; MO, monocytes cultured in Teflon beakers for 3-7 d; PD, PBS without divalent cations; phorbol dibutyrate; PDFCS, PD containing 1% FCS.