title: Increased phagocyte Fc gammaRI expression and improved Fc gamma-receptor-mediated phagocytosis after in vivo recombinant human interferon-gamma treatment of normal human subjects.
abstract: Recombinant human interferon-gamma (rhIFN-gamma) 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-gamma. 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 Fc gamma-receptor (Fc gammaRI) was observed that peaked 48 hours after the initiation of rhIFN-gamma treatment (P < .05). Monocyte expression of Fc gammaRI, Fc gammaRII, Fc gammaRIII, 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-gamma treatment (P < .05) and correlated with Fc gammaRI expression by neutrophils (r = .8, P < .001). This increase in ingestion could be inhibited by anti-Fc gammaRI monoclonal antibodies. Levels of the serum opsonin lipopolysaccharide-binding protein also significantly increased after in vivo rhIFN-gamma (P < .05). These results suggest that the protective effect of rhIFN-gamma in patients with CGD may involve improved microbial clearance. Moreover, improved phagocyte trafficking may occur secondary to increased expression of monocyte beta2-integrins. Because these IFN-gamma-related improvements in host defense were seen in normal hosts, rhIFN-gamma may have broader applications in the treatment of various disorders of immunity in addition to its demonstrated efficacy in CGD.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Schiff
authors.forename: J
authors.initials: J
authors.lastname: Rae
authors.forename: T R
authors.initials: TR
authors.lastname: Martin
authors.forename: B H
authors.initials: BH
authors.lastname: Davis
authors.forename: J T
authors.initials: JT
authors.lastname: Curnutte
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009895:Opsonin Proteins / Q000097:blood; D010586:Phagocytes / Q000378:metabolism*; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D000209:Acute-Phase Proteins; D000970:Antineoplastic Agents; D018950:Lipopolysaccharide Receptors; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C091196:opsonin receptor; D007371:Interferon-gamma