Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Feb;65(2):557–563. doi: 10.1128/iai.65.2.557-563.1997

Cryptococcal polysaccharides bind to CD18 on human neutrophils.

Z M Dong 1, J W Murphy 1
PMCID: PMC176096  PMID: 9009313

Abstract

CD18, the beta chain of the beta 2 integrin family of adhesion molecules, is associated with three different alpha chains (CD11a, -b, and -c) and is expressed on the surface of all types of leukocytes. CD18-containing molecules are up-regulated on the surface of neutrophils (polymorphonuclear cells [PMN]) in response to chemotactic agents and are implicated in mediating adhesion to an inflamed endothelium, which is a prerequisite to migration of PMN into infected tissues. In a previous study, we found that a cryptococcal culture filtrate (CneF), when injected into the bloodstream of mice to simulate the antigenemia in cryptococcosis, inhibits PMN accumulation at the site of an inflammatory stimulus. In the present study, we assessed the ability of CneF and its individual components, i.e., glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoprotein (MP), to interact with CD18 on human PMN. CneF labeled with 14C was shown to bind to human PMN in a dose-dependent manner. Pretreatment of PMN with anti-CD18, but not an isotype-matched control monoclonal antibody (MAb) or anti-CD11a MAb, blocked the binding of 14C-labeled CneF to PMN. In addition, CneF, GXM, and GalXM but not MP significantly blocked the binding of the anti-CD18 MAb to CD18 on the surface of unactivated and formyl methionyl leucyl phenylalanine-activated PMN as determined by indirect immunofluorescence staining and flow cytometric analysis. In the same experiments, the cryptococcal polysaccharides did not affect the binding of an anti-CD11a or anti-L-selectin MAb to the surface of PMN at 4 degrees C. The results suggest that CneF and its components GXM and GalXM bind to CD18 on human PMN. Based on our findings, we propose that CD18 is a possible molecular target of cryptococcal polysaccharides and that binding of the polysaccharides to CD18 has the potential to inhibit leukocyte infiltration into inflammatory sites.

Full Text

The Full Text of this article is available as a PDF (243.2 KB).

Selected References

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

  1. Anderson D. C., Springer T. A. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175–194. doi: 10.1146/annurev.me.38.020187.001135. [DOI] [PubMed] [Google Scholar]
  2. Arbonés M. L., Ord D. C., Ley K., Ratech H., Maynard-Curry C., Otten G., Capon D. J., Tedder T. F. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity. 1994 Jul;1(4):247–260. doi: 10.1016/1074-7613(94)90076-0. [DOI] [PubMed] [Google Scholar]
  3. Arfors K. E., Lundberg C., Lindbom L., Lundberg K., Beatty P. G., Harlan J. M. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 1987 Jan;69(1):338–340. [PubMed] [Google Scholar]
  4. Bazil V., Strominger J. L. Metalloprotease and serine protease are involved in cleavage of CD43, CD44, and CD16 from stimulated human granulocytes. Induction of cleavage of L-selectin via CD16. J Immunol. 1994 Feb 1;152(3):1314–1322. [PubMed] [Google Scholar]
  5. Buchanan K. L., Murphy J. W. Characterization of cellular infiltrates and cytokine production during the expression phase of the anticryptococcal delayed-type hypersensitivity response. Infect Immun. 1993 Jul;61(7):2854–2865. doi: 10.1128/iai.61.7.2854-2865.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  8. Carlos T. M., Harlan J. M. Leukocyte-endothelial adhesion molecules. Blood. 1994 Oct 1;84(7):2068–2101. [PubMed] [Google Scholar]
  9. Carlos T. M., Harlan J. M. Membrane proteins involved in phagocyte adherence to endothelium. Immunol Rev. 1990 Apr;114:5–28. doi: 10.1111/j.1600-065x.1990.tb00559.x. [DOI] [PubMed] [Google Scholar]
  10. Cherniak R., Sundstrom J. B. Polysaccharide antigens of the capsule of Cryptococcus neoformans. Infect Immun. 1994 May;62(5):1507–1512. doi: 10.1128/iai.62.5.1507-1512.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Diamond R. D., Bennett J. E. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med. 1974 Feb;80(2):176–181. doi: 10.7326/0003-4819-80-2-176. [DOI] [PubMed] [Google Scholar]
  12. Dong Z. M., Murphy J. W. Cryptococcal polysaccharides induce L-selectin shedding and tumor necrosis factor receptor loss from the surface of human neutrophils. J Clin Invest. 1996 Feb 1;97(3):689–698. doi: 10.1172/JCI118466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dong Z. M., Murphy J. W. Intravascular cryptococcal culture filtrate (CneF) and its major component, glucuronoxylomannan, are potent inhibitors of leukocyte accumulation. Infect Immun. 1995 Mar;63(3):770–778. doi: 10.1128/iai.63.3.770-778.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dong Z. M., Murphy J. W. Mobility of human neutrophils in response to Cryptococcus neoformans cells, culture filtrate antigen, and individual components of the antigen. Infect Immun. 1993 Dec;61(12):5067–5077. doi: 10.1128/iai.61.12.5067-5077.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eng R. H., Bishburg E., Smith S. M., Kapila R. Cryptococcal infections in patients with acquired immune deficiency syndrome. Am J Med. 1986 Jul;81(1):19–23. doi: 10.1016/0002-9343(86)90176-2. [DOI] [PubMed] [Google Scholar]
  16. Farmer S. G., Komorowski R. A. Histologic response to capsule-deficient Cryptococcus neoformans. Arch Pathol. 1973 Dec;96(6):383–387. [PubMed] [Google Scholar]
  17. Hechtman D. H., Cybulsky M. I., Fuchs H. J., Baker J. B., Gimbrone M. A., Jr Intravascular IL-8. Inhibitor of polymorphonuclear leukocyte accumulation at sites of acute inflammation. J Immunol. 1991 Aug 1;147(3):883–892. [PubMed] [Google Scholar]
  18. Isberg R. R., Tran Van Nhieu G. Binding and internalization of microorganisms by integrin receptors. Trends Microbiol. 1994 Jan;2(1):10–14. doi: 10.1016/0966-842x(94)90338-7. [DOI] [PubMed] [Google Scholar]
  19. Jutila M. A. Function and regulation of leukocyte homing receptors. J Leukoc Biol. 1994 Jan;55(1):133–140. doi: 10.1002/jlb.55.1.133. [DOI] [PubMed] [Google Scholar]
  20. Jutila M. A., Rott L., Berg E. L., Butcher E. C. Function and regulation of the neutrophil MEL-14 antigen in vivo: comparison with LFA-1 and MAC-1. J Immunol. 1989 Nov 15;143(10):3318–3324. [PubMed] [Google Scholar]
  21. Kishimoto T. K., Jutila M. A., Berg E. L., Butcher E. C. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science. 1989 Sep 15;245(4923):1238–1241. doi: 10.1126/science.2551036. [DOI] [PubMed] [Google Scholar]
  22. Luscinskas F. W., Kiely J. M., Ding H., Obin M. S., Hébert C. A., Baker J. B., Gimbrone M. A., Jr In vitro inhibitory effect of IL-8 and other chemoattractants on neutrophil-endothelial adhesive interactions. J Immunol. 1992 Sep 15;149(6):2163–2171. [PubMed] [Google Scholar]
  23. Mills J., Masur H. AIDS-related infections. Sci Am. 1990 Aug;263(2):50–57. doi: 10.1038/scientificamerican0890-50. [DOI] [PubMed] [Google Scholar]
  24. Mosser D. M., Springer T. A., Diamond M. S. Leishmania promastigotes require opsonic complement to bind to the human leukocyte integrin Mac-1 (CD11b/CD18). J Cell Biol. 1992 Jan;116(2):511–520. doi: 10.1083/jcb.116.2.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Murphy J. W., Mosley R. L., Cherniak R., Reyes G. H., Kozel T. R., Reiss E. Serological, electrophoretic, and biological properties of Cryptococcus neoformans antigens. Infect Immun. 1988 Feb;56(2):424–431. doi: 10.1128/iai.56.2.424-431.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Reiss E., Cherniak R., Eby R., Kaufman L. Enzyme immunoassay detection of IgM to galactoxylomannan of Cryptococcus neoformans. Diagn Immunol. 1984;2(2):109–115. [PubMed] [Google Scholar]
  27. Rogers M. F., Thomas P. A., Starcher E. T., Noa M. C., Bush T. J., Jaffe H. W. Acquired immunodeficiency syndrome in children: report of the Centers for Disease Control National Surveillance, 1982 to 1985. Pediatrics. 1987 Jun;79(6):1008–1014. [PubMed] [Google Scholar]
  28. Sanchez-Madrid F., Nagy J. A., Robbins E., Simon P., Springer T. A. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. doi: 10.1084/jem.158.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Simonet W. S., Hughes T. M., Nguyen H. Q., Trebasky L. D., Danilenko D. M., Medlock E. S. Long-term impaired neutrophil migration in mice overexpressing human interleukin-8. J Clin Invest. 1994 Sep;94(3):1310–1319. doi: 10.1172/JCI117450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith C. W., Marlin S. D., Rothlein R., Toman C., Anderson D. C. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest. 1989 Jun;83(6):2008–2017. doi: 10.1172/JCI114111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Tuomanen E. I., Saukkonen K., Sande S., Cioffe C., Wright S. D. Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes. J Exp Med. 1989 Sep 1;170(3):959–969. doi: 10.1084/jem.170.3.959. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES