POSTTRANSLATIONAL UP-REGULATION OF THE CELL SURFACE-ASSOCIATED ALPHA-COMPONENT OF THE HUMAN TYPE-I INTERFERON RECEPTOR DURING DIFFERENTIATION OF PERIPHERAL-BLOOD MONOCYTES - ROLE IN THE BIOLOGICAL RESPONSE TO TYPE-I INTERFERON

Human peripheral blood monocytes cultured in vitro exhibit a greater s ensitivity to the antiviral effect of type I interferon (IFN) compared to freshly isolated monocytes. We evaluated the effect of macrophage differentiation on the expression of type I IFN receptors (IFN-R). Bin ding studies with iodinated IFN-alpha 2 and Scatchard plot analysis re vealed that a single class of high-affinity receptors was present in f reshly isolated monocytes. Monocyte differentiation to macrophages res ulted in a three- to fourfold increase in the number of cell surface r eceptors with no change in their affinity. Polymerase chain reaction a nalysis of RNA revealed that comparable levels of mRNA for the IFN-R a lpha (IFNAR1) and LFNAR2 components were expressed in freshly isolated monocytes and 7-day cultured macrophages. Likewise, the levels of IFN AR1 protein remained constant over time in culture. Immunofluorescence studies revealed that IFNAR1 was localized in intracellular compartme nts of freshly isolated monocytes, whereas it was predominantly detect ed on the cell surface in 7-day cultured macrophages. The increased ex pression of IFN-R on the plasma membrane of cultured macrophages may, at least in part, account for the increased antiviral efect of type I IFN in these cells. These modifications represent one of the events oc curring during monocyte differentiation that may play a role in the re gulation of macrophage functions.