Neutrophil Fc gamma RI expression as a determinant of oxidative responses in human blood

PurposeNeutrophils express Fc receptors on their surface to trap immune complexes. While the implication 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 upregulation and reactive oxygen species (ROS) generation, but the biological relevance of this process is still unclear. MethodsBlood samples were obtained from healthy volunteers and patients with lupus. Aggregated IgGs were prepared as a model of immune complex. Fc{gamma}Rs surface expression on circulating leukocytes and on freshly isolated neutrophils was measured by flow cytometry. ROS production was monitored with luminol-based chemiluminescence. ResultsIncubation of blood samples from healthy volunteers with aggregated IgGs rapidly upregulated the surface expression of Fc{gamma}RI, predominantly on neutrophils. Stimulation of isolated neutrophils from healthy donors with aggregated IgGs resulted in the production of ROS in an Fc{gamma}RI-dependent fashion. Cytochalasin B potentiated Fc{gamma}RI expression and ROS production. Positive correlations between neutrophil Fc{gamma}RI and ROS production were observed in resting blood from both healthy volunteers and lupus patients. In the lupus cohort, monocyte Fc{gamma}RI also correlated with ROS production. ConclusionThis study unveils a previously underappreciated role for neutrophil Fc{gamma}RI in ROS production in both healthy individuals and patients with lupus, and identifies Fc{gamma}RI as a potential biomarker of oxidative response.