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. 1987 Mar;79(3):715–720. doi: 10.1172/JCI112876

Demonstration of defective C3-receptor-mediated clearance by the reticuloendothelial system in patients with acquired immunodeficiency syndrome.

B S Bender, J F Bohnsack, S H Sourlis, M M Frank, T C Quinn
PMCID: PMC424182  PMID: 3546375

Abstract

The function of macrophage C3 receptors was assessed in vivo by measuring the clearance of C3-sensitized autologous erythrocytes in seven acquired immunodeficiency syndrome (AIDS) patients, eight healthy homosexual men, eight healthy heterosexual men, and four infected controls. Healthy heterosexual men had an initial clearance of 50.1 +/- 2.0% of the inoculum, with a release of a small portion of these cells (10.9 +/- 1.3%) into the circulation. Healthy homosexual men had a greater initial clearance of 66.0 +/- 4.2% (P less than 0.01) followed by a similar release (14.0 +/- 3.3%). AIDS patients had an initial clearance of 60.6 +/- 7.5% but had a relatively large release of cells (25.6 +/- 3.2%) (P less than 0.005 vs. heterosexuals; P less than 0.05 vs. homosexuals), suggesting a failure of macrophage phagocytosis. Infected controls had an initial clearance of 59.4 +/- 4.9%, with a release of 19.6 +/- 3.8% (P = NS vs. AIDS). These data, in addition to Fc-receptor dysfunction, demonstrate a global reticuloendothelial system dysfunction in AIDS patients. This may contribute to their frequent infections with opportunistic pathogens and inappropriate immune responses against these microorganisms.

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Selected References

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  1. Atkinson J. P., Frank M. M. Studies on the in vivo effects of antibody. Interaction of IgM antibody and complement in the immune clearance and destruction of erythrocytes in man. J Clin Invest. 1974 Aug;54(2):339–348. doi: 10.1172/JCI107769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Atkinson J. P., Frank M. M. The effect of Bacillus Calmette-Guerin-induced macrophage activation on the in vivo clearance of sensitized erythrocytes. J Clin Invest. 1974 Jun;53(6):1742–1749. doi: 10.1172/JCI107726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bender B. S., Auger F. A., Quinn T. C., Redfield R., Gold J., Folks T. M. Impaired antibody-dependent cell-mediated cytotoxic activity in patients with the acquired immunodeficiency syndrome. Clin Exp Immunol. 1986 Apr;64(1):166–172. [PMC free article] [PubMed] [Google Scholar]
  4. Bender B. S., Frank M. M., Lawley T. J., Smith W. J., Brickman C. M., Quinn T. C. Defective reticuloendothelial system Fc-receptor function in patients with acquired immunodeficiency syndrome. J Infect Dis. 1985 Aug;152(2):409–412. doi: 10.1093/infdis/152.2.409. [DOI] [PubMed] [Google Scholar]
  5. Broder S., Gallo R. C. A pathogenic retrovirus (HTLV-III) linked to AIDS. N Engl J Med. 1984 Nov 15;311(20):1292–1297. doi: 10.1056/NEJM198411153112006. [DOI] [PubMed] [Google Scholar]
  6. Chess Q., Daniels J., North E., Macris N. T. Serum immunoglobulin elevations in the acquired immunodeficiency syndrome (AIDS): IgG, IgA, IgM, and IgD. Diagn Immunol. 1984;2(3):148–153. [PubMed] [Google Scholar]
  7. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  8. Fahey J. L., Prince H., Weaver M., Groopman J., Visscher B., Schwartz K., Detels R. Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders. Am J Med. 1984 Jan;76(1):95–100. doi: 10.1016/0002-9343(84)90756-3. [DOI] [PubMed] [Google Scholar]
  9. Fauci A. S. Immunologic abnormalities in the acquired immunodeficiency syndrome (AIDS). Clin Res. 1984 Dec;32(5):491–499. [PubMed] [Google Scholar]
  10. Fauci A. S., Macher A. M., Longo D. L., Lane H. C., Rook A. H., Masur H., Gelmann E. P. NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med. 1984 Jan;100(1):92–106. doi: 10.7326/0003-4819-100-1-92. [DOI] [PubMed] [Google Scholar]
  11. Frank M. M., Lawley T. J., Hamburger M. I., Brown E. J. NIH Conference: Immunoglobulin G Fc receptor-mediated clearance in autoimmune diseases. Ann Intern Med. 1983 Feb;98(2):206–218. doi: 10.7326/0003-4819-98-2-218. [DOI] [PubMed] [Google Scholar]
  12. Gaither T. A., Hammer C. H., Frank M. M. Studies of the molecular mechanisms of C3b inactivation and a simplified assay of beta 1H and the C3b inactivator (C3bINA). J Immunol. 1979 Sep;123(3):1195–1204. [PubMed] [Google Scholar]
  13. Gaither T. A., Hammer C. H., Gadek J. E., Katusha K., Santaella M., Frank M. M. Cleavage of membrane-bound C3b and C3bi by viable human neutrophils (PMN). Mol Immunol. 1983 Jun;20(6):623–635. doi: 10.1016/0161-5890(83)90007-x. [DOI] [PubMed] [Google Scholar]
  14. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  15. Gonda M. A., Wong-Staal F., Gallo R. C., Clements J. E., Narayan O., Gilden R. V. Sequence homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science. 1985 Jan 11;227(4683):173–177. doi: 10.1126/science.2981428. [DOI] [PubMed] [Google Scholar]
  16. Gyorkey F., Melnick J. L., Sinkovics J. G., Gyorkey P. Retrovirus resembling HTLV in macrophages of patients with AIDS. Lancet. 1985 Jan 12;1(8420):106–106. doi: 10.1016/s0140-6736(85)91995-6. [DOI] [PubMed] [Google Scholar]
  17. Jaffe C. J., Vierling J. M., Jones E. A., Lawley T. J., Frank M. M. Receptor specific clearance by the reticuloendothelial system in chronic liver diseases. Demonstration of defective C3b-specific clearance in primary biliary cirrhosis. J Clin Invest. 1978 Nov;62(5):1069–1077. doi: 10.1172/JCI109212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
  19. Kornfeld H., Vande Stouwe R. A., Lange M., Reddy M. M., Grieco M. H. T-lymphocyte subpopulations in homosexual men. N Engl J Med. 1982 Sep 16;307(12):729–731. doi: 10.1056/NEJM198209163071206. [DOI] [PubMed] [Google Scholar]
  20. Kostianovsky M., Kang Y. H., Grimley P. M. Disseminated tubuloreticular inclusions in acquired immunodeficiency syndrome (AIDS). Ultrastruct Pathol. 1983 Jun;4(4):331–336. doi: 10.3109/01913128309140585. [DOI] [PubMed] [Google Scholar]
  21. Levy J. A., Shimabukuro J., McHugh T., Casavant C., Stites D., Oshiro L. AIDS-associated retroviruses (ARV) can productively infect other cells besides human T helper cells. Virology. 1985 Dec;147(2):441–448. doi: 10.1016/0042-6822(85)90146-1. [DOI] [PubMed] [Google Scholar]
  22. McDougal J. S., Hubbard M., Nicholson J. K., Jones B. M., Holman R. C., Roberts J., Fishbein D. B., Jaffe H. W., Kaplan J. E., Spira T. J. Immune complexes in the acquired immunodeficiency syndrome (AIDS): relationship to disease manifestation, risk group, and immunologic defect. J Clin Immunol. 1985 Mar;5(2):130–138. doi: 10.1007/BF00915011. [DOI] [PubMed] [Google Scholar]
  23. Murray H. W., Rubin B. Y., Masur H., Roberts R. B. Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med. 1984 Apr 5;310(14):883–889. doi: 10.1056/NEJM198404053101404. [DOI] [PubMed] [Google Scholar]
  24. Narayan O., Wolinsky J. S., Clements J. E., Strandberg J. D., Griffin D. E., Cork L. C. Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats. J Gen Virol. 1982 Apr;59(Pt 2):345–356. doi: 10.1099/0022-1317-59-2-345. [DOI] [PubMed] [Google Scholar]
  25. Pinching A. J., McManus T. J., Jeffries D. J., Moshtael O., Donaghy M., Parkin J. M., Munday P. E., Harris J. R. Studies of cellular immunity in male homosexuals in London. Lancet. 1983 Jul 16;2(8342):126–130. doi: 10.1016/s0140-6736(83)90115-0. [DOI] [PubMed] [Google Scholar]
  26. Prince H. E., Moody D. J., Shubin B. I., Fahey J. L. Defective monocyte function in acquired immune deficiency syndrome (AIDS): evidence from a monocyte-dependent T-cell proliferative system. J Clin Immunol. 1985 Jan;5(1):21–25. doi: 10.1007/BF00915164. [DOI] [PubMed] [Google Scholar]
  27. Rankin J. A., Walzer P. D., Dwyer J. M., Schrader C. E., Enriquez R. E., Merrill W. W. Immunologic alterations in bronchoalveolar lavage fluid in the acquired immunodeficiency syndrome (AIDS). Am Rev Respir Dis. 1983 Jul;128(1):189–194. doi: 10.1164/arrd.1983.128.1.189. [DOI] [PubMed] [Google Scholar]
  28. Schreiber A. D., Frank M. M. Role of antibody and complement in the immune clearance and destruction of erythrocytes. I. In vivo effects of IgG and IgM complement-fixing sites. J Clin Invest. 1972 Mar;51(3):575–582. doi: 10.1172/JCI106846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Seligmann M., Chess L., Fahey J. L., Fauci A. S., Lachmann P. J., L'Age-Stehr J., Ngu J., Pinching A. J., Rosen F. S., Spira T. J. AIDS--an immunologic reevaluation. N Engl J Med. 1984 Nov 15;311(20):1286–1292. doi: 10.1056/NEJM198411153112005. [DOI] [PubMed] [Google Scholar]
  30. Smith P. D., Ohura K., Masur H., Lane H. C., Fauci A. S., Wahl S. M. Monocyte function in the acquired immune deficiency syndrome. Defective chemotaxis. J Clin Invest. 1984 Dec;74(6):2121–2128. doi: 10.1172/JCI111637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spivak J. L., Bender B. S., Quinn T. C. Hematologic abnormalities in the acquired immune deficiency syndrome. Am J Med. 1984 Aug;77(2):224–228. doi: 10.1016/0002-9343(84)90695-8. [DOI] [PubMed] [Google Scholar]
  32. Stahl R. E., Friedman-Kien A., Dubin R., Marmor M., Zolla-Pazner S. Immunologic abnormalities in homosexual men. Relationship to Kaposi's sarcoma. Am J Med. 1982 Aug;73(2):171–178. doi: 10.1016/0002-9343(82)90174-7. [DOI] [PubMed] [Google Scholar]
  33. Tausk F. A., McCutchan A., Spechko P., Schreiber R. D., Gigli I. Altered erythrocyte C3b receptor expression, immune complexes, and complement activation in homosexual men in varying risk groups for acquired immune deficiency syndrome. J Clin Invest. 1986 Oct;78(4):977–982. doi: 10.1172/JCI112688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Venet A., Dennewald G., Sandron D., Stern M., Jaubert F., Leibowitch J. Bronchoalveolar lavage in acquired immunodeficiency syndrome. Lancet. 1983 Jul 2;2(8340):53–53. doi: 10.1016/s0140-6736(83)90041-7. [DOI] [PubMed] [Google Scholar]
  35. Washburn R. G., Tuazon C. U., Bennett J. E. Phagocytic and fungicidal activity of monocytes from patients with acquired immunodeficiency syndrome. J Infect Dis. 1985 Mar;151(3):565–566. doi: 10.1093/infdis/151.3.565. [DOI] [PubMed] [Google Scholar]

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