Skip to main content
Log in

Dysfunctional monocytes from a patient with disseminatedMycobacterium kansasii infection are activatedin vitro andin vivo by GM-CSF

  • Published:
Biotherapy

Abstract

A 27 year-old woman presented with disseminated infection due toMycobacterium kansasii. Signs and symptoms of disseminated infection persisted despite the administration of multiple antimycobacterial agents to which her organism was sensitive for 15 months. She was seronegative for HIV-1 and functional studies of T and B lymphocytes and granulocytes failed to demonstrate any abnormality. Peripheral blood monocytes proved abnormally permissive to the intracellular growth ofMycobacterium avium andM. kansasii, and expressed normal number of receptors to interferon-gamma, but reduced numbers of receptors to granulocyte monocyte colony stimulating factor and tumor necrosis factor. These defects were partially reversed within vitro exposure of her cells to recombinant GM-CSF. In addition, administration of recombinant human GM-CSFin vivo (250 mg/M2 per day) for 10 days armed her circulating monocytes as evidenced by increased production of O2 in response to phorbol esther and, when infectedex vivo withM. kansasii, enhanced inhibition of intracellular growth compared with pre-therapy monocytes. These defects reappeared with discontinuation of GM-CSF and resolved with its re-administration. While a salutary clinical and microbiologic effect was difficult to assess, administration of GM-CSFin vivo was associated within vitro activation of monocytes and enhanced mycobactericidal activity in this patient with a defect in monocyte function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Woods GL, Washington JA 2nd. Mycobacteria other thanMycobacterium tuberculosis: Review of microbiologic and clinical aspects. Rev Infect Dis 1987; 9: 275–294.

    PubMed  Google Scholar 

  2. Wolinsky E. Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 1979; 119: 107–182.

    Google Scholar 

  3. Schraufnagel D, Leach J, Pollak B.Mycobacterium kansasii: Colonization and disease. Br J Dis Chest 1986; 80: 131–137.

    PubMed  Google Scholar 

  4. Francis P, Jay S, Johanson WJ. The course of untreatedM. kansasii disease. Am Rev Respir Dis 1975; 111: 477–483.

    PubMed  Google Scholar 

  5. Ahn C, Wallace RJ, Steele L, Murphy D. Sulfonamide-containing regimens for disease caused by rifampin-resistantMycobacterium kansasii. Am Rev Respir Dis 1987; 135: 10–16.

    PubMed  Google Scholar 

  6. Pezzia W, Raleigh J, Bailey M, Toth E, Silverblatt J. Treatment of pulmonary disease due toMycobacterium kansasii: Recent experiences with rifampin. Rev Infect Dis 1981; 3: 1035–1039.

    PubMed  Google Scholar 

  7. Sutker WL, Lankford LL, Tompsett R. Granulomatous synovitis: The role of atypical mycobacteria. Rev Infect Dis 1979; 729–735.

  8. Yangco B, Espinoza C, Germain B. Nontuberculous mycobacterial joint infections. In: Espinoza, A, Goldenberg, A, eds. Infections in the rheumatic diseases. W.B. Saunders (Philadelphia) 1988; 139–157.

    Google Scholar 

  9. Hagmar B, Kuttie J, Lundin P. Disseminated infection caused byM. kansasii disease: Report of a case and brief review of the literature. Acta Med Scand 1969; 186: 93–105.

    PubMed  Google Scholar 

  10. McGeady S, Murphey S. DisseminatedMycobacterium kansasii infection. Clin Immunol Immunopathol 1981; 20: 87–98.

    PubMed  Google Scholar 

  11. Lincoln EM, Gilbert LA. Disease in children due to mycobacteria other thanMycobacterium tuberculosis. Am Rev Respir Dis 1972; 105: 683–714.

    PubMed  Google Scholar 

  12. Lichtenstein I, MacGregor R. Mycobacterial infections in renal transplant recipients: Report of five cases and review of the literature. Rev Infect Dis 1983; 5: 216–226.

    PubMed  Google Scholar 

  13. Bennett C. Disseminated atypical mycobacterial infection in patients with hairy cell leukemia. Am J Med 1986; 80: 891–896.

    PubMed  Google Scholar 

  14. Carpenter J, Parks J.Mycobacterium kansasii infections in patients positive for human immunodeficiency virus. Rev Infect Dis 1991; 13: 789–796.

    PubMed  Google Scholar 

  15. Horsburgh CJ, Selik R. The epidemiology of disseminated mycobacterial infection in the acquired immunodeficiency syndrome. Am Rev Respir Dis 1989; 139: 4–7.

    PubMed  Google Scholar 

  16. Levine B, Chaisson R.Mycobacterium kansasii: A cause of treatable pulmonary disease associated with advanced human immunodeficiency virus infection. Ann Intern Med 1991; 114: 861–868.

    PubMed  Google Scholar 

  17. Nakagawara A, Nathan C. A simple method for counting adherent cells: Application to cultured human monocytes, macrophages and multinucleated giant cells. J Immunol Methods 1983; 56: 261–264.

    PubMed  Google Scholar 

  18. Bermudez L, Young L. Recombinant granulocyte-macrophage colony stimulating factor activates human macrophages to inhibit growth or killMycobacterium avium complex. J Leukocyte Biol 1990; 48: 67–74.

    PubMed  Google Scholar 

  19. Bermudez L, Young L. Tumor necrosis factor, alone or in combination with IL-2, but not IFN-gamma, is associated with macrophage killing ofMycobacterium avium complex. J immunol 1988; 140: 3006–3013.

    PubMed  Google Scholar 

  20. Metcalf D. The molecular biology and function of granulocyte macrophage colony-stimulating factors. Blood 1986; 67: 257–263.

    PubMed  Google Scholar 

  21. Gamble JR, Elliot MJ, Jaipargas E, Lopez AF. Regulation of human monocyte adherence by granulocyte-macrophage colony-stimulating factor. Proc Nat Acad Sci (USA) 1989; 86: 7169–7173.

    Google Scholar 

  22. Djeu JY, Serboursek D, Smith-Joyner M, Blanchard DK. Enhancement of anti-tumor activity in human polymorphonuclear neutrophils (PMN) and monocytes by granulocytemacrophage colony-stimulating factor. Fed Proc 1987: 1511–1516.

  23. Grabstein KH, Urdal DL, Tushinski RJ, Mochizuki DY, Price VL, Cantrell MA, Gillis S, Conlon PJ. Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor. Science 1986; 232: 506–508.

    PubMed  Google Scholar 

  24. Cannistra SA, Vellenga E, Grosheck P, Rambaldi A, Griffin JD. Human granulocyte-monocyte colony-stimulating factor and interleukin-3 stimulate monocyte cytotoxicity through a tumor necrosis factor-dependent mechanism. Blood 1988; 71: 672–676.

    PubMed  Google Scholar 

  25. Reed SG, Nathan CF, Pihl DL, Rodricks P, Shanebeck K, Conlon PJ, Grabstein KH. Recombinant granulocyte-macrophage colony-stimulating factor activates macrophages to inhibitTrypanosoma cruzi and release hydrogen peroxide. J Exp Med 1987; 166: 1734–1742.

    PubMed  Google Scholar 

  26. Denis M, Gregg EO. Recombinant tumor necrosis factor-alpha decreases whereas recombinant interleukin-6 increases growth of a virulent strain ofMycobacterium avium in human macrophages. Immunology 1990; 71: 139–141.

    PubMed  Google Scholar 

  27. Bermudez LE, Stevens P, Kolonoski P, Wu M, Young LS. Treatment of experimental disseminatedMycobacterium avium complex infection in mice with recombinant IL-2 and tumor necrosis factor. J Immunol 1989; 143: 2996–3000.

    PubMed  Google Scholar 

  28. Wing EJ, Magee M, Whiteside TL, Kaplan SS, Shadduck RK. Recombinant human granulocyte/macrophage colony-stimulating factor enhances monocyte cytotoxicity and secretion of tumor necrosis factor a and interferon in cancerpatients. Blood 1989; 73: 643–646.

    PubMed  Google Scholar 

  29. Bermudez LE, Marinelli J, Petrofski M, Kolonoski P, Young LS. Recombinant granulocyte-macrophage colony stimulating factor enhances the effects of antibiotics againstMycobacterium avium complex in the beige mouse model. J Infect Dis 1994; 169: 575–80.

    PubMed  Google Scholar 

  30. Kleinerman ES, Knowles RD, Lachmann LB, Gutterman JU. Effect of recombinant granulocyte/macrophage colony-stimulating factor on human monocyte activityin vitro and following intravenous administration. Cancer Res 1988; 48: 2604–2609.

    PubMed  Google Scholar 

  31. Perkins RC, Vadhan-Raj S, Scheule RK, Hamilton R, Holian A. Effects of continuous high dose rhGM-CSF infusion on human monocyte activity. Am J Hematol 1993; 279–285.

  32. Bermudez LE, Enkel H, Young LS. Role of cell wall proteins in the pathogenesis ofMycobacterium avium complex infection. In: Program Abstr. 29th Intersc. Conf. Antimicrob. Agents Chemother. Washington D.C., 1989.

  33. Ostergaard GZ, Nielsen H, Friis B. Defective monocyte oxidative metabolism in a child with Smith-Lemli-Opitz syndrome. Eur J Pediatr 1992; 151: 291–294.

    PubMed  Google Scholar 

  34. Fisher A, Virelizier JL, Griscelli C, Durandy A, Nezelof C, Trung PH. Defective monocyte functions in a child with fatal disseminated BCG infection. Clin Immunol Immunopathol 1980; 17: 296–306.

    PubMed  Google Scholar 

  35. Herlin T, Thelle T, Kragballe K, Borregaard N, Thestrup-Pederson K. Sustained depression of monocyte cytotoxicity in a boy with disseminated nontuberculous mycobacteriosis. J Pediatr 1981; 99: 264–267.

    PubMed  Google Scholar 

  36. Uchiyama N, Greene GR, Warren BJ, Morozumi PA, Spear GS, Galant SP. Possible monocyte killing defect in familial atypical mycobacteriosis. J Pediatr 1981; 98: 785–788.

    PubMed  Google Scholar 

  37. Holland SM, Eisenstein EM, Kuhns DB, Turner ML, Fleisher TA, Strober W, Gallin JI. Treatment of refractory disseminated nontuberculous mycobacterial infection with interferon gamma: A preliminary report. N Engl J Med 1994; 330: 1348–1355.

    PubMed  Google Scholar 

  38. Harshan KV, Gangadharam PRJ.In vivo depletion of natural killer cell activity leads to enhanced multiplication ofMycobacterium avium complex in mice. Infect Immun 1991; 59: 2818–2821.

    PubMed  Google Scholar 

  39. Bermudez LEM, Young LS. Natural killer cell-dependent mycobacteriostatic and mycobactericidal activity in human macrophages. J Immunol 1991; 146: 265–270.

    PubMed  Google Scholar 

  40. Katz P, Yeager H Jr., Whalen G, Evans M, Swartz RP, Roecklein J. Natural killer cell-mediated lysis ofMycobacterium avium complex infected monocytes. J Clin Immunol 1990; 10: 71–77.

    PubMed  Google Scholar 

  41. Blanchard DK, Micheline-Norris MB, Friedman H, Djeu JY. Lysis of mycobacteria-infected monocytes by IL-2 activated killer cells: Role of LFA-1. Cell Immunol 1989; 119: 402–411.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bermudez, L.E., Kemper, C.A. & Deresinski, S.C. Dysfunctional monocytes from a patient with disseminatedMycobacterium kansasii infection are activatedin vitro andin vivo by GM-CSF. Biotherapy 8, 135–142 (1994). https://doi.org/10.1007/BF01878497

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01878497

Keywords

Navigation