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Increased Phagocyte Fc RI Expression and Improved Fc-Receptor-Mediated Phagocytosis After In Vivo Recombinant Human Interferon- Treatment of Normal Human Subjects
Deborah E. Schiff,
Julie Rae,
Thomas R. Martin,
Bruce H. Davis, and
John T. Curnutte
From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; the Medical Research Service, Seattle Veterans Affairs Medical Center, Seattle, WA; and the Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, MI.
Recombinant human interferon- (rhIFN-) 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-. 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-receptor (FcRI) was observed that peaked 48 hours after the initiation of rhIFN- treatment (P < .05). Monocyte expression of FcRI, FcRII, FcRIII, 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- treatment (P < .05) and correlated with FcRI expression by neutrophils (r = .8, P < .001). This increase in ingestion could be inhibited by anti-FcRI monoclonal antibodies. Levels of the serum opsonin lipopolysaccharide-binding protein also significantly increased after in vivo rhIFN- (P < .05). These results suggest that the protective effect of rhIFN- in patients with CGD may involve improved microbial clearance. Moreover, improved phagocyte trafficking may occur secondary to increased expression of monocyte  2 -integrins. Because these IFN--related improvements in host defense were seen in normal hosts, rhIFN- may have broader applications in the treatment of various disorders of immunity in addition to its demonstrated efficacy in CGD.
Blood, Vol. 90 No. 8 (July 15), 1997:
pp. 3187-3194
© 1997 by The American Society of Hematology.
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