Abstract
Although gamma interferon (IFN-gamma) exerts profound effects on the state of activation of macrophages, its influence on receptor-mediated phagocytosis and killing of extracellular bacteria is poorly understood. Human monocytes cultured in the presence of human recombinant IFN-gamma exhibited an enhanced capacity to produce superoxide anion. Although these cells bound greater numbers of particles via Fc receptors, their capacity to phagocytose by these receptors or to bind or ingest particles via receptors for C3bi, mannose, or unopsonized Pseudomonas aeruginosa was substantially depressed in a dose-dependent fashion (0.1 to 1,000 U of IFN-gamma per ml). Macrophage phagocytosis of P. aeruginosa and Staphylococcus aureus opsonized with whole serum or with serum deficient in immunoglobulin or complement was also depressed. Macrophages cultured in the presence of IFN-gamma had a diminished capacity to kill both unopsonized and opsonized P. aeruginosa. We conclude that IFN-gamma inhibits macrophage nonopsonic and opsonic receptor-mediated phagocytosis and killing but enhances oxidative radical generation; its production may exacerbate host tissue damage during chronic infection with extracellular pathogens.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Badaro R., Falcoff E., Badaro F. S., Carvalho E. M., Pedral-Sampaio D., Barral A., Carvalho J. S., Barral-Netto M., Brandely M., Silva L. Treatment of visceral leishmaniasis with pentavalent antimony and interferon gamma. N Engl J Med. 1990 Jan 4;322(1):16–21. doi: 10.1056/NEJM199001043220104. [DOI] [PubMed] [Google Scholar]
- Basham T. Y., Merigan T. C. Recombinant interferon-gamma increases HLA-DR synthesis and expression. J Immunol. 1983 Apr;130(4):1492–1494. [PubMed] [Google Scholar]
- Becker S. Interferons as modulators of human monocyte-macrophage differentiation. I. Interferon-gamma increases HLA-DR expression and inhibits phagocytosis of zymosan. J Immunol. 1984 Mar;132(3):1249–1254. [PubMed] [Google Scholar]
- Byrd T. F., Horwitz M. A. Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. J Clin Invest. 1989 May;83(5):1457–1465. doi: 10.1172/JCI114038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Douvas G. S., Looker D. L., Vatter A. E., Crowle A. J. Gamma interferon activates human macrophages to become tumoricidal and leishmanicidal but enhances replication of macrophage-associated mycobacteria. Infect Immun. 1985 Oct;50(1):1–8. doi: 10.1128/iai.50.1.1-8.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edwards S. W., Say J. E., Hughes V. Gamma interferon enhances the killing of Staphylococcus aureus by human neutrophils. J Gen Microbiol. 1988 Jan;134(1):37–42. doi: 10.1099/00221287-134-1-37. [DOI] [PubMed] [Google Scholar]
- Ezekowitz R. A., Dinauer M. C., Jaffe H. S., Orkin S. H., Newburger P. E. Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med. 1988 Jul 21;319(3):146–151. doi: 10.1056/NEJM198807213190305. [DOI] [PubMed] [Google Scholar]
- Ezekowitz R. A., Orkin S. H., Newburger P. E. Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous disease gene expression in X-linked variant chronic granulomatous disease. J Clin Invest. 1987 Oct;80(4):1009–1016. doi: 10.1172/JCI113153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldberg M., Belkowski L. S., Bloom B. R. Regulation of macrophage function by interferon-gamma. Somatic cell genetic approaches in murine macrophage cell lines to mechanisms of growth inhibition, the oxidative burst, and expression of the chronic granulomatous disease gene. J Clin Invest. 1990 Feb;85(2):563–569. doi: 10.1172/JCI114473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guyre P. M., Morganelli P. M., Miller R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest. 1983 Jul;72(1):393–397. doi: 10.1172/JCI110980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jungi T. W., Lerch P. G., Brcic M. The effect of recombinant interferon-gamma on human monocyte-derived macrophages. Eur J Immunol. 1987 May;17(5):735–738. doi: 10.1002/eji.1830170526. [DOI] [PubMed] [Google Scholar]
- Jungi T. W., Rüegg S. J., Morell A. Interferon gamma-treated human macrophages display enhanced cytolysis and generation of reactive oxygen metabolites but reduced ingestion upon Fc receptor triggering. Hum Immunol. 1989 Feb;24(2):77–93. doi: 10.1016/0198-8859(89)90049-9. [DOI] [PubMed] [Google Scholar]
- Kemmerich B., Rossing T. H., Pennington J. E. Comparative oxidative microbicidal activity of human blood monocytes and alveolar macrophages and activation by recombinant gamma interferon. Am Rev Respir Dis. 1987 Aug;136(2):266–270. doi: 10.1164/ajrccm/136.2.266. [DOI] [PubMed] [Google Scholar]
- Mokoena T., Gordon S. Human macrophage activation. Modulation of mannosyl, fucosyl receptor activity in vitro by lymphokines, gamma and alpha interferons, and dexamethasone. J Clin Invest. 1985 Feb;75(2):624–631. doi: 10.1172/JCI111740. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray H. W. Interferon-gamma, the activated macrophage, and host defense against microbial challenge. Ann Intern Med. 1988 Apr;108(4):595–608. doi: 10.7326/0003-4819-108-4-595. [DOI] [PubMed] [Google Scholar]
- Nathan C. F., Kaplan G., Levis W. R., Nusrat A., Witmer M. D., Sherwin S. A., Job C. K., Horowitz C. R., Steinman R. M., Cohn Z. A. Local and systemic effects of intradermal recombinant interferon-gamma in patients with lepromatous leprosy. N Engl J Med. 1986 Jul 3;315(1):6–15. doi: 10.1056/NEJM198607033150102. [DOI] [PubMed] [Google Scholar]
- Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perussia B., Dayton E. T., Lazarus R., Fanning V., Trinchieri G. Immune interferon induces the receptor for monomeric IgG1 on human monocytic and myeloid cells. J Exp Med. 1983 Oct 1;158(4):1092–1113. doi: 10.1084/jem.158.4.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quie P. G., White J. G., Holmes B., Good R. A. In vitro bactericidal capacity of human polymorphonuclear leukocytes: diminished activity in chronic granulomatous disease of childhood. J Clin Invest. 1967 Apr;46(4):668–679. doi: 10.1172/JCI105568. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sechler J. M., Malech H. L., White C. J., Gallin J. I. Recombinant human interferon-gamma reconstitutes defective phagocyte function in patients with chronic granulomatous disease of childhood. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4874–4878. doi: 10.1073/pnas.85.13.4874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Speert D. P., Eftekhar F., Puterman M. L. Nonopsonic phagocytosis of strains of Pseudomonas aeruginosa from cystic fibrosis patients. Infect Immun. 1984 Mar;43(3):1006–1011. doi: 10.1128/iai.43.3.1006-1011.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Speert D. P., Loh B. A., Cabral D. A., Salit I. E. Nonopsonic phagocytosis of nonmucoid Pseudomonas aeruginosa by human neutrophils and monocyte-derived macrophages is correlated with bacterial piliation and hydrophobicity. Infect Immun. 1986 Jul;53(1):207–212. doi: 10.1128/iai.53.1.207-212.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Speert D. P., Silverstein S. C. Phagocytosis of unopsonized zymosan by human monocyte-derived macrophages: maturation and inhibition by mannan. J Leukoc Biol. 1985 Nov;38(5):655–658. doi: 10.1002/jlb.38.5.655. [DOI] [PubMed] [Google Scholar]
- Speert D. P., Wright S. D., Silverstein S. C., Mah B. Functional characterization of macrophage receptors for in vitro phagocytosis of unopsonized Pseudomonas aeruginosa. J Clin Invest. 1988 Sep;82(3):872–879. doi: 10.1172/JCI113692. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weening R. S., Wever R., Roos D. Quantitative aspects of the production of superoxide radicals by phagocytizing human granulocytes. J Lab Clin Med. 1975 Feb;85(2):245–252. [PubMed] [Google Scholar]
- Wright S. D., Detmers P. A., Jong M. T., Meyer B. C. Interferon-gamma depresses binding of ligand by C3b and C3bi receptors on cultured human monocytes, an effect reversed by fibronectin. J Exp Med. 1986 May 1;163(5):1245–1259. doi: 10.1084/jem.163.5.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wright S. D., Silverstein S. C. Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. J Exp Med. 1982 Oct 1;156(4):1149–1164. doi: 10.1084/jem.156.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van GELDER B., SLATER E. C. The extinction coefficient of cytochrome c. Biochim Biophys Acta. 1962 Apr 23;58:593–595. doi: 10.1016/0006-3002(62)90073-2. [DOI] [PubMed] [Google Scholar]