Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. 1985 December; 76(6): 2196–2205.
PMCID: PMC424342

Demonstration and partial characterization of the interferon-gamma receptor on human mononuclear phagocytes.


Radioiodinated recombinant human interferon-gamma (IFN gamma) bound to human monocytes, U937, and HL60 cells in a specific, saturable, and reversible manner. At 4 degrees C, the different cell types bound 3,000-7,000 molecules of IFN gamma, and binding was of comparable affinity (Ka = 4-12 X 10(8) M-1). No change in the receptor was observed after monocytes differentiated to macrophages or when the cell lines were pharmacologically induced to differentiate. The functional relevance of the receptor was validated by the demonstration that receptor occupancy correlated with induction of Fc receptors on U937. Binding studies using U937 permeabilized with digitonin showed that only 46% of the total receptor pool was expressed at the cell surface. The receptor appears to be a protein, since treatment of U937 with trypsin or pronase reduced 125I-IFN gamma binding by 87 and 95%, respectively. At 37 degrees C, ligand was internalized, since 32% of the cell-associated IFN gamma became resistant to trypsin stripping. Monocytes degraded 125I-IFN gamma into trichloroacetic acid-soluble counts at 37 degrees C but not at 4 degrees C, at an approximate rate of 5,000 molecules/cell per h. The receptor was partially characterized by SDS-polyacrylamide gel electrophoresis analysis of purified U937 membranes that had been incubated with 125I-IFN gamma. After cross-linking, the receptor-ligand complex migrated as a broad band that displayed an Mr of 104,000 +/- 18,000 at the top and 84,000 +/- 6,000 at the bottom. These results thereby define and partially characterize the IFN gamma receptor of human mononuclear phagocytes.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • North RJ. The concept of the activated macrophage. J Immunol. 1978 Sep;121(3):806–809. [PubMed]
  • Karnovsky ML, Lazdins JK. Biochemical criteria for activated macrophages. J Immunol. 1978 Sep;121(3):809–813. [PubMed]
  • Cohn ZA. Activation of mononuclear phagocytes: fact, fancy, and future. J Immunol. 1978 Sep;121(3):813–816. [PubMed]
  • Rocklin RE, Bendtzen K, Greineder D. Mediators of immunity: lymphokines and monokines. Adv Immunol. 1980;29:55–136. [PubMed]
  • Celada A, Gray PW, Rinderknecht E, Schreiber RD. Evidence for a gamma-interferon receptor that regulates macrophage tumoricidal activity. J Exp Med. 1984 Jul 1;160(1):55–74. [PMC free article] [PubMed]
  • Schreiber RD, Hicks LJ, Celada A, Buchmeier NA, Gray PW. Monoclonal antibodies to murine gamma-interferon which differentially modulate macrophage activation and antiviral activity. J Immunol. 1985 Mar;134(3):1609–1618. [PubMed]
  • Schreiber RD, Altman A, Katz DH. Identification of a T cell hybridoma that produces large quantities of macrophage-activating factor. J Exp Med. 1982 Sep 1;156(3):677–689. [PMC free article] [PubMed]
  • Blalock JE, Georgiades JA, Langford MP, Johnson HM. Purified human immune interferon has more potent anticellular activity than fibroblast or leukocyte interferon. Cell Immunol. 1980 Feb;49(2):390–394. [PubMed]
  • Gray PW, Leung DW, Pennica D, Yelverton E, Najarian R, Simonsen CC, Derynck R, Sherwood PJ, Wallace DM, Berger SL, et al. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503–508. [PubMed]
  • Pangburn MK, Schreiber RD, Müller-Eberhard HJ. Deficiency of an erythrocyte membrane protein with complement regulatory activity in paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5430–5434. [PubMed]
  • Sundström C, Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. [PubMed]
  • Collins SJ, Gallo RC, Gallagher RE. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. [PubMed]
  • Jesaitis AJ, Naemura JR, Painter RG, Sklar LA, Cochrane CG. Intracellular localization of N-formyl chemotactic receptor and Mg2+ dependent ATPase in human granulocytes. Biochim Biophys Acta. 1982 Dec 17;719(3):556–568. [PubMed]
  • Jesaitis AJ, Naemura JR, Painter RG, Sklar LA, Cochrane CG. The fate of an N-formylated chemotactic peptide in stimulated human granulocytes. Subcellular fractionation studies. J Biol Chem. 1983 Feb 10;258(3):1968–1977. [PubMed]
  • Weigel PH, Oka JA. The large intracellular pool of asialoglycoprotein receptors functions during the endocytosis of asialoglycoproteins by isolated rat hepatocytes. J Biol Chem. 1983 Apr 25;258(8):5095–5102. [PubMed]
  • Fischer HD, Gonzalez-Noriega A, Sly WS, Morré DJ. Phosphomannosyl-enzyme receptors in rat liver. Subcellular distribution and role in intracellular transport of lysosomal enzymes. J Biol Chem. 1980 Oct 25;255(20):9608–9615. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Wright SD, Silverstein SC. 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. [PMC free article] [PubMed]
  • Radzun HJ, Parwaresch MR, Sundström C, Nilsson K, Eissner M. Monocytic origin of the human hematopoietic cell line U-937 and its convertibility to macrophages evidenced by isoenzyme mapping. Int J Cancer. 1983 Feb 15;31(2):181–186. [PubMed]
  • Rovera G, Santoli D, Damsky C. Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2779–2783. [PubMed]
  • Collins SJ, Ruscetti FW, Gallagher RE, Gallo RC. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci U S A. 1978 May;75(5):2458–2462. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Perussia B, Dayton ET, 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. [PMC free article] [PubMed]
  • Guyre PM, Morganelli PM, Miller R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest. 1983 Jul;72(1):393–397. [PMC free article] [PubMed]
  • Buessow SC, Gillespie GY. Interferon-alpha and -gamma promote myeloid differentiation of HL-60, a human acute promyelocytic leukemia cell line. J Biol Response Mod. 1984 Dec;3(6):653–662. [PubMed]
  • Hattori T, Pack M, Bougnoux P, Chang ZL, Hoffman T. Interferon-induced differentiation of U937 cells. Comparison with other agents that promote differentiation of human myeloid or monocytelike cell lines. J Clin Invest. 1983 Jul;72(1):237–244. [PMC free article] [PubMed]
  • Weinberg JB, Hobbs MM, Misukonis MA. Recombinant human gamma-interferon induces human monocyte polykaryon formation. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4554–4557. [PubMed]
  • Fleit HB, Wright SD, Durie CJ, Valinsky JE, Unkeless JC. Ontogeny of Fc receptors and complement receptor (CR3) during human myeloid differentiation. J Clin Invest. 1984 Feb;73(2):516–525. [PMC free article] [PubMed]
  • Nathan CF, Murray HW, Wiebe ME, Rubin BY. 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. [PMC free article] [PubMed]
  • Marino PA, Adams DO. The capacity of activated murine macrophages for augmented binding of neoplastic cells: analysis of induction by lymphokine containing MAF and kinetics of the reaction. J Immunol. 1982 Jun;128(6):2816–2823. [PubMed]
  • Meltzer MS, Occhionero M, Ruco LP. Macrophage activation for tumor cytotoxicity: regulatory mechanisms for induction and control of cytotoxic activity. Fed Proc. 1982 Apr;41(6):2198–2205. [PubMed]
  • Occhionero M, Leonard EJ, Meltzer MS. Functional characterization of lymphokines from the EL-4 T cell line that activate macrophages for nonspecific tumor cytotoxicity. J Leukoc Biol. 1984 Apr;35(4):405–414. [PubMed]
  • Dianzani F, Salter L, Fleischmann WR, Jr, Zucca M. Immune interferon activates cells more slowly than does virus-induced interferon. Proc Soc Exp Biol Med. 1978 Oct;159(1):94–97. [PubMed]
  • Anderson P, Yip YK, Vilcek J. Specific binding of 125I-human interferon-gamma to high affinity receptors on human fibroblasts. J Biol Chem. 1982 Oct 10;257(19):11301–11304. [PubMed]
  • Anderson P, Yip YK, Vilcek J. Human interferon-gamma is internalized and degraded by cultured fibroblasts. J Biol Chem. 1983 May 25;258(10):6497–6502. [PubMed]
  • Sarkar FH, Gupta SL. Receptors for human gamma interferon: binding and crosslinking of 125I-labeled recombinant human gamma interferon to receptors on WISH cells. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5160–5164. [PubMed]
  • Orchansky P, Novick D, Fischer DG, Rubinstein M. Type I and Type II interferon receptors. J Interferon Res. 1984 Spring;4(2):275–282. [PubMed]
  • Littman SJ, Faltynek CR, Baglioni C. Binding of human recombinant 125I-interferon gamma to receptors on human cells. J Biol Chem. 1985 Jan 25;260(2):1191–1195. [PubMed]
  • Thompson MR, Zhang Z, Fournier A, Tan YH. Characterization of human beta-interferon-binding sites on human cells. J Biol Chem. 1985 Jan 10;260(1):563–567. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation