Differentiation of the human monocyte cell line, U937, with dibutyryl cyclicAMP induces the expression of the inhibitory Fc receptor, FcγRIIb

Abstract

FC receptor for IgG receptor (Fcγ) mediated activation of macrophages is essential for the clearance of immune complexes and control of inflammation. However, activated macrophages play an integral role in tissue destruction associated with autoimmune and inflammatory disease processes. Understanding the mechanisms which balance activating and inhibitory signals generated by immune complexes are therefore of critical importance to human disease. Here, we demonstrate that differentiation of the human monocytic U937 cell line to a macrophage phenotype with dibutyryl cyclicAMP induces both mRNA and protein expression of the inhibitory IgG receptor, FcγRIIb1. We further demonstrate that, following receptor aggregation, FcγRII transiently recruits the 5′-inositol phosphatase, SHIP. These data define a role for FcγRIIb in the modulation of immune complex mediated macrophage activation in a human model system.