Neutrophil Fc gamma RI expression as a determinant of oxidative responses in human blood
Sandrine HuotiD, Paul R. FortiniD, Cynthia LaflammeiD, Marc PouliotiD
Abstract
Neutrophils express Fc receptors on their surface to trap immune complexes. While the roles of Fc{gamma}RIIa and Fc{gamma}RIIIb have extensively been studied in that context, that of Fc{gamma}RI remains elusive. Recently, aggregated IgGs have been shown to induce rapid Fc{gamma}RI 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 Fc{gamma}RI, predominantly on neutrophils, as measured by flow cytometry. Stimulation of isolated neutrophils with aggregated IgGs resulted in the production of ROS in an Fc{gamma}RI-dependent fashion, as monitored with a luminol-based chemiluminescence assay. Cytochalasin B potentiated Fc{gamma}RI expression and ROS production. In resting blood, positive correlations between neutrophil Fc{gamma}RI and ROS production were observed, both in healthy volunteers and patients with lupus. This study unveils a potentially central regulatory role for neutrophil Fc{gamma}RI in ROS production, both in healthy individuals and patients with lupus, and identifies neutrophil Fc{gamma}RI as a promising target to modulate oxidative response.
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