Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1993 Feb;61(2):663–670. doi: 10.1128/iai.61.2.663-670.1993

Mycobacterium avium-M. intracellulare binds to the integrin receptor alpha v beta 3 on human monocytes and monocyte-derived macrophages.

S P Rao 1, K Ogata 1, A Catanzaro 1
PMCID: PMC302778  PMID: 7678588

Abstract

Mycobacterium avium-M. intracellulare is an intracellular pathogen responsible for the highest incidence of disseminated bacterial infection in patients with AIDS. Treatment of the infection is difficult and has been of limited efficacy. Attachment of the organism to macrophages is a critical early step in the establishment of the disease. In the present study, we isolated and identified a receptor that mediates attachment of M. avium-M. intracellulare to human peripheral blood monocytes and monocyte-derived macrophages. On Western blotting, (immunoblotting), the receptor was found to cross-react with antibodies against a human vitronectin receptor (alpha v beta 3). The receptor could be purified from monocyte extracts by using monoclonal antibodies (MAbs) against the alpha v subunit of vitronectin receptor coupled to CNBr-Sepharose 4B, as well as with the adhesive tripeptide sequence arginine-glycine-aspartic acid (RGD) coupled to CNBr-Sepharose 4B. Surface-bound MAbs directed against alpha v beta 3 were found to inhibit the attachment of M. avium-M. intracellulare to monocyte-derived macrophages in an in vitro inhibition assay, while MAbs directed against CD14, CD18, alpha 2 beta 1 and platelet glycoprotein gpIIb/IIIa receptors did not inhibit this attachment. These observations suggest that alpha v beta 3 on the surface of human monocytes and monocyte-derived macrophages may function as a receptor for M. avium-M. intracellulare. Identification of a receptor for M. avium-M. intracellulare on macrophages may offer new approaches to the prevention and control of M. avium-M. intracellulare infection at the cellular level.

Full text

PDF
670

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albelda S. M., Buck C. A. Integrins and other cell adhesion molecules. FASEB J. 1990 Aug;4(11):2868–2880. [PubMed] [Google Scholar]
  2. Armstrong D., Gold J. W., Dryjanski J., Whimbey E., Polsky B., Hawkins C., Brown A. E., Bernard E., Kiehn T. E. Treatment of infections in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):738–743. doi: 10.7326/0003-4819-103-5-738. [DOI] [PubMed] [Google Scholar]
  3. Barksdale L., Kim K. S. Mycobacterium. Bacteriol Rev. 1977 Mar;41(1):217–372. doi: 10.1128/br.41.1.217-372.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bermudez L. E., Young L. S., Enkel H. Interaction of Mycobacterium avium complex with human macrophages: roles of membrane receptors and serum proteins. Infect Immun. 1991 May;59(5):1697–1702. doi: 10.1128/iai.59.5.1697-1702.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bullock W. E., Wright S. D. Role of the adherence-promoting receptors, CR3, LFA-1, and p150,95, in binding of Histoplasma capsulatum by human macrophages. J Exp Med. 1987 Jan 1;165(1):195–210. doi: 10.1084/jem.165.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cardarelli P. M., Pierschbacher M. D. Identification of fibronectin receptors on T lymphocytes. J Cell Biol. 1987 Jul;105(1):499–506. doi: 10.1083/jcb.105.1.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Catanzaro A., Wright S. D. Binding of Mycobacterium avium-Mycobacterium intracellulare to human leukocytes. Infect Immun. 1990 Sep;58(9):2951–2956. doi: 10.1128/iai.58.9.2951-2956.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Charo I. F., Bekeart L. S., Phillips D. R. Platelet glycoprotein IIb-IIIa-like proteins mediate endothelial cell attachment to adhesive proteins and the extracellular matrix. J Biol Chem. 1987 Jul 25;262(21):9935–9938. [PubMed] [Google Scholar]
  9. Cheresh D. A., Harper J. R. Arg-Gly-Asp recognition by a cell adhesion receptor requires its 130-kDa alpha subunit. J Biol Chem. 1987 Feb 5;262(4):1434–1437. [PubMed] [Google Scholar]
  10. Cheresh D. A. Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6471–6475. doi: 10.1073/pnas.84.18.6471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cheresh D. A., Spiro R. C. Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. J Biol Chem. 1987 Dec 25;262(36):17703–17711. [PubMed] [Google Scholar]
  12. Chiu J., Nussbaum J., Bozzette S., Tilles J. G., Young L. S., Leedom J., Heseltine P. N., McCutchan J. A. Treatment of disseminated Mycobacterium avium complex infection in AIDS with amikacin, ethambutol, rifampin, and ciprofloxacin. California Collaborative Treatment Group. Ann Intern Med. 1990 Sep 1;113(5):358–361. doi: 10.7326/0003-4819-113-5-358. [DOI] [PubMed] [Google Scholar]
  13. Crowle A. J., Poche P. Inhibition by normal human serum of Mycobacterium avium multiplication in cultured human macrophages. Infect Immun. 1989 Apr;57(4):1332–1335. doi: 10.1128/iai.57.4.1332-1335.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Damsker B., Bottone E. J. Mycobacterium avium-Mycobacterium intracellulare from the intestinal tracts of patients with the acquired immunodeficiency syndrome: concepts regarding acquisition and pathogenesis. J Infect Dis. 1985 Jan;151(1):179–181. doi: 10.1093/infdis/151.1.179. [DOI] [PubMed] [Google Scholar]
  15. Dautzenberg B., Truffot C., Legris S., Meyohas M. C., Berlie H. C., Mercat A., Chevret S., Grosset J. Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. A controlled clinical trial. Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):564–569. doi: 10.1164/ajrccm/144.3_Pt_1.564. [DOI] [PubMed] [Google Scholar]
  16. Gehlsen K. R., Dillner L., Engvall E., Ruoslahti E. The human laminin receptor is a member of the integrin family of cell adhesion receptors. Science. 1988 Sep 2;241(4870):1228–1229. doi: 10.1126/science.2970671. [DOI] [PubMed] [Google Scholar]
  17. Gehlsen K. R., Sriramarao P., Furcht L. T., Skubitz A. P. A synthetic peptide derived from the carboxy terminus of the laminin A chain represents a binding site for the alpha 3 beta 1 integrin. J Cell Biol. 1992 Apr;117(2):449–459. doi: 10.1083/jcb.117.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Haass C., Koo E. H., Mellon A., Hung A. Y., Selkoe D. J. Targeting of cell-surface beta-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. Nature. 1992 Jun 11;357(6378):500–503. doi: 10.1038/357500a0. [DOI] [PubMed] [Google Scholar]
  19. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  20. Iseman M. D., Corpe R. F., O'Brien R. J., Rosenzwieg D. Y., Wolinsky E. Disease due to Mycobacterium avium-intracellulare. Chest. 1985 Feb;87(2 Suppl):139S–149S. doi: 10.1378/chest.87.2.139s. [DOI] [PubMed] [Google Scholar]
  21. Lamb F. I., Singh N. B., Colston M. J. The specific 18-kilodalton antigen of Mycobacterium leprae is present in Mycobacterium habana and functions as a heat-shock protein. J Immunol. 1990 Mar 1;144(5):1922–1925. [PubMed] [Google Scholar]
  22. Leong J. M., Fournier R. S., Isberg R. R. Identification of the integrin binding domain of the Yersinia pseudotuberculosis invasin protein. EMBO J. 1990 Jun;9(6):1979–1989. doi: 10.1002/j.1460-2075.1990.tb08326.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lisanti M. P., Sargiacomo M., Graeve L., Saltiel A. R., Rodriguez-Boulan E. Polarized apical distribution of glycosyl-phosphatidylinositol-anchored proteins in a renal epithelial cell line. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9557–9561. doi: 10.1073/pnas.85.24.9557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mapother M. E., Songer J. G. In vitro interaction of Mycobacterium avium with intestinal epithelial cells. Infect Immun. 1984 Jul;45(1):67–73. doi: 10.1128/iai.45.1.67-73.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Michl J., Pieczonka M. M., Unkeless J. C., Bell G. I., Silverstein S. C. Fc receptor modulation in mononuclear phagocytes maintained on immobilized immune complexes occurs by diffusion of the receptor molecule. J Exp Med. 1983 Jun 1;157(6):2121–2139. doi: 10.1084/jem.157.6.2121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pischel K. D., Hemler M. E., Huang C., Bluestein H. G., Woods V. L., Jr Use of the monoclonal antibody 12F1 to characterize the differentiation antigen VLA-2. J Immunol. 1987 Jan 1;138(1):226–233. [PubMed] [Google Scholar]
  27. Pytela R., Pierschbacher M. D., Ruoslahti E. A 125/115-kDa cell surface receptor specific for vitronectin interacts with the arginine-glycine-aspartic acid adhesion sequence derived from fibronectin. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5766–5770. doi: 10.1073/pnas.82.17.5766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Relman D., Tuomanen E., Falkow S., Golenbock D. T., Saukkonen K., Wright S. D. Recognition of a bacterial adhesion by an integrin: macrophage CR3 (alpha M beta 2, CD11b/CD18) binds filamentous hemagglutinin of Bordetella pertussis. Cell. 1990 Jun 29;61(7):1375–1382. doi: 10.1016/0092-8674(90)90701-f. [DOI] [PubMed] [Google Scholar]
  29. Ruoslahti E., Pierschbacher M. D. Arg-Gly-Asp: a versatile cell recognition signal. Cell. 1986 Feb 28;44(4):517–518. doi: 10.1016/0092-8674(86)90259-x. [DOI] [PubMed] [Google Scholar]
  30. Ruoslahti E., Pierschbacher M. D. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. doi: 10.1126/science.2821619. [DOI] [PubMed] [Google Scholar]
  31. Savill J., Dransfield I., Hogg N., Haslett C. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature. 1990 Jan 11;343(6254):170–173. doi: 10.1038/343170a0. [DOI] [PubMed] [Google Scholar]
  32. Schlesinger L. S., Bellinger-Kawahara C. G., Payne N. R., Horwitz M. A. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J Immunol. 1990 Apr 1;144(7):2771–2780. [PubMed] [Google Scholar]
  33. Suzuki S., Argraves W. S., Pytela R., Arai H., Krusius T., Pierschbacher M. D., Ruoslahti E. cDNA and amino acid sequences of the cell adhesion protein receptor recognizing vitronectin reveal a transmembrane domain and homologies with other adhesion protein receptors. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8614–8618. doi: 10.1073/pnas.83.22.8614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Swartz R. P., Naai D., Vogel C. W., Yeager H., Jr Differences in uptake of mycobacteria by human monocytes: a role for complement. Infect Immun. 1988 Sep;56(9):2223–2227. doi: 10.1128/iai.56.9.2223-2227.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Talamás-Rohana P., Wright S. D., Lennartz M. R., Russell D. G. Lipophosphoglycan from Leishmania mexicana promastigotes binds to members of the CR3, p150,95 and LFA-1 family of leukocyte integrins. J Immunol. 1990 Jun 15;144(12):4817–4824. [PubMed] [Google Scholar]
  36. Wallace J. M., Hannah J. B. Mycobacterium avium complex infection in patients with the acquired immunodeficiency syndrome. A clinicopathologic study. Chest. 1988 May;93(5):926–932. doi: 10.1378/chest.93.5.926. [DOI] [PubMed] [Google Scholar]
  37. Woods V. L., Jr, Oh E. H., Mason D., McMillan R. Autoantibodies against the platelet glycoprotein IIb/IIIa complex in patients with chronic ITP. Blood. 1984 Feb;63(2):368–375. [PubMed] [Google Scholar]
  38. Wright S. D., Rao P. E., Van Voorhis W. C., Craigmyle L. S., Iida K., Talle M. A., Westberg E. F., Goldstein G., Silverstein S. C. Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699–5703. doi: 10.1073/pnas.80.18.5699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Young L. S., Inderlied C. B., Berlin O. G., Gottlieb M. S. Mycobacterial infections in AIDS patients, with an emphasis on the Mycobacterium avium complex. Rev Infect Dis. 1986 Nov-Dec;8(6):1024–1033. doi: 10.1093/clinids/8.6.1024. [DOI] [PubMed] [Google Scholar]
  41. Young L. S. Mycobacterium avium complex infection. J Infect Dis. 1988 May;157(5):863–867. doi: 10.1093/infdis/157.5.863. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES