FcγRIIa is a target for modulation by TNFα in human neutrophils

Activation of neutrophils by the interaction of immune complexes with Fc gamma receptors (Fc gamma R) is amplified in tumor necrosis factor-alpha (TNF alpha)-primed cells, whereas interleukin-10 (IL-10) has been reported to suppress cytokine-mediated neutrophil activation. We examined whether the expression and function of Fc gamma R in human neutrophils is modulated by TNFa and IL-10 in vitro, and whether Fc gamma RIIa expression is altered following treatment with the TNF alpha inhibitor infliximab in rheumatoid arthritis (RA) patients in vivo. TNF alpha treatment induced upregulation of expression and function of the major activating Fc receptor, Fc gamma RIIa, in neutrophils from healthy donors. Unexpectedly, treatment with IL-10 led to gain of Fc gamma RIIa function in TNF alpha-primed neutrophils. In neutrophils from RA patients initiating infliximab therapy and followed longitudinally through consecutive treatments, Fc gamma RIIa protein decreased during the course of TNF alpha blockade, indicating that Fc gamma RIIa is a target of TNF alpha modulation in human neutrophils in vivo. (c) 2005 Elsevier Inc. All rights reserved.