Neutrophil FcγRI expression as a determinant of oxidative responses in human blood.

Abstract

Neutrophils express Fc receptors on their surface to trap immune complexes. While the roles of FcγRIIa and FcγRIIIb have been extensively studied in that context, that of FcγRI remains elusive. Recently, aggregated IgGs have been shown to induce rapid FcγRI up-regulation and reactive oxygen species (ROS) generation, but the biological relevance of this process is still unclear. In this study, incubation of blood samples from healthy volunteers with heat-aggregated IgGs, used as a model of immune complexes, rapidly up-regulated the surface expression of FcγRI, predominantly on neutrophils, as measured by flow cytometry. Stimulation of isolated neutrophils with aggregated IgGs resulted in the production of ROS in an FcγRI-dependent fashion, as monitored with a luminol-based chemiluminescence assay. Cytochalasin B potentiated FcγRI expression and ROS production. In resting blood, positive correlations between neutrophil FcγRI and ROS production were observed, both in healthy volunteers and patients with lupus. This study unveils a potentially central regulatory role for neutrophil FcγRI in ROS production, both in healthy individuals and patients with lupus, and identifies neutrophil FcγRI as a promising target to modulate oxidative response.