Increased Phagocyte FcγRI Expression and Improved Fcγ-Receptor–Mediated Phagocytosis After In Vivo Recombinant Human Interferon-γ Treatment of Normal Human Subjects

Abstract

Recombinant human interferon-γ (rhIFN-γ) decreases the frequency of serious infections in patients with chronic granulomatous disease (CGD) through an unknown mechanism. To test the hypothesis that it exerts a beneficial effect by enhancing clearance of microbes from the bloodstream and tissues, normal human subjects were treated in vivo with rhIFN-γ. Phagocyte opsonic receptor expression, serum opsonin levels, and phagocytosis of bacteria were then measured. A 4.7-fold increase in neutrophil expression of the high-affinity Fcγ-receptor (FcγRI) was observed that peaked 48 hours after the initiation of rhIFN-γ treatment (P < .05). Monocyte expression of FcγRI, FcγRII, FcγRIII, CD11a, CD11b, CD18, and HLA-DR also significantly increased with peak expression at 48 hours. Phagocytosis by neutrophils of killed Staphylococcus aureus opsonized with heat-inactivated pooled human serum significantly improved after rhIFN-γ treatment (P < .05) and correlated with FcγRI expression by neutrophils (r = .8, P < .001). This increase in ingestion could be inhibited by anti-FcγRI monoclonal antibodies. Levels of the serum opsonin lipopolysaccharide-binding protein also significantly increased after in vivo rhIFN-γ (P < .05). These results suggest that the protective effect of rhIFN-γ in patients with CGD may involve improved microbial clearance. Moreover, improved phagocyte trafficking may occur secondary to increased expression of monocyte β2 -integrins. Because these IFN-γ–related improvements in host defense were seen in normal hosts, rhIFN-γ may have broader applications in the treatment of various disorders of immunity in addition to its demonstrated efficacy in CGD.

Interferon‐γ in healthy subjects: selective modulation of inflammatory mediators

“…The percentage of neutrophils expressing FcgRI increased after IFN-g administration, whereas no effect was measured on the MFI of FcgRI on neutrophils. The latter finding is in contrast to the study by Schiff et al [43], who administered IFN-g (50 mg m 22 day 21 ) to healthy subjects for 2 days, and noticed an increased MFI of FCgRI expression on neutrophils. We have no clear explanation for these different results, except that Schiff injected less IFN-g.…”

Platelet-specific hemophagocytosis in a patient with juvenile dermatomyositis

“…These ®ndings are consistent with previous studies demonstrating the pathological roles of both humoral and cell-mediated immunity in DM (9). Furthermore, IFN-g is a potential activator of macrophage and enhances the expression of FcgR (10). It is therefore possible that the production of PA-IgG, activation of macrophage and subsequent FcgR-mediated hemophagocytosis occurred as a result of underlying DM.…”

Human IgG isotypes and activating Fcγ receptors in the interaction of Salmonella enterica serovar Typhimurium with phagocytic cells

“…62 Furthermore, FccRI is highly competent in phagocytosis, 63 and important in the uptake of bactaeremia-causing bacteria such as Staphylococcus aureus by human neutrophils. 64 However, FccRIIA-transfected non-phagocytic cells are able to phagocytose Escherichia coli efficiently 65 and we found that IgG2-mediated bacterial uptake has a greater dependency on FccRIIA over FccRI. Hence, both FccRI and FccRIIA are important in mediating phagocytosis in THP-1 cells, and the relative importance of each FccR differs, depending on the antibody subclass in question.…”