Purpose: Neutrophils 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. Methods: Blood samples were obtained from healthy volunteers and patients with lupus. Aggregated IgGs were prepared as a model of immune complex. Fc gamma receptor surface expression on circulating leukocytes and on freshly isolated neutrophils was measured by flow cytometry. ROS production was monitored with luminol-based chemiluminescence. Results: Incubation 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. Conclusion: This 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.
Huot et al. (Wed,) studied this question.