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. 1988 Feb;56(2):363–369. doi: 10.1128/iai.56.2.363-369.1988

Roles of CR3 and mannose receptors in the attachment and ingestion of Leishmania donovani by human mononuclear phagocytes.

M E Wilson 1, R D Pearson 1
PMCID: PMC259289  PMID: 2962944

Abstract

Leishmania donovani is an obligate intracellular parasite of mammalian macrophages. Two macrophage receptors, the mannose-fucose receptor (MFR) and the receptor for complement component C3bi, CR3, were examined for their roles in the attachment and ingestion of L. donovani by human monocyte-derived macrophages. Two monoclonal antibodies which bind to the human CR3, anti-Mo1 and anti-Mac-1, inhibited both attachment and ingestion of L. donovani promastigotes after preincubation with human monocyte-derived macrophages; attachment was inhibited by 40 and 62% by anti-Mo1 and anti-Mac-1, respectively, and ingestion was inhibited by 34 and 51% by anti-Mo1 and anti-Mac-1, respectively. The interaction between promastigotes and CR3 may not have involved the C3bi-binding site on CR3, however, because a monoclonal antibody which exhibits specificity for this site, OKM10, inhibited promastigote attachment by only 18%. In contrast, OKM1, which is believed to react with the alternate lectinlike binding site on CR3, inhibited ingestion by 65%. MFR activity was inhibited using the soluble MFR ligands, mannan and mannosylated bovine serum albumin, which also inhibited promastigote attachment by 40 and 37%, respectively. The simultaneous inhibition of both CR3 (by anti-Mac-1) and the MFR (by either mannan or mannosylated bovine serum albumin) resulted in a greater decrease in promastigote attachment than inhibition of either receptor alone. Additionally, the reduction of MFR activity by allowing macrophages to adhere to a mannan-coated surface followed by the addition of anti-CR3 antibodies resulted in an 81% inhibition of promastigote ingestion, a greater decrease than was obtained by manipulation of either receptor alone. The results suggest that the MFR and CR3 independently participate in the attachment and ingestion of L. donovani promastigotes by human macrophages.

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Selected References

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  1. Beller D. I., Springer T. A., Schreiber R. D. Anti-Mac-1 selectively inhibits the mouse and human type three complement receptor. J Exp Med. 1982 Oct 1;156(4):1000–1009. doi: 10.1084/jem.156.4.1000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berton G., Gordon S. Modulation of macrophage mannosyl-specific receptors by cultivation on immobilized zymosan. Effects on superoxide-anion release and phagocytosis. Immunology. 1983 Aug;49(4):705–715. [PMC free article] [PubMed] [Google Scholar]
  3. Blackwell J. M., Ezekowitz R. A., Roberts M. B., Channon J. Y., Sim R. B., Gordon S. Macrophage complement and lectin-like receptors bind Leishmania in the absence of serum. J Exp Med. 1985 Jul 1;162(1):324–331. doi: 10.1084/jem.162.1.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bouvier J., Etges R. J., Bordier C. Identification and purification of membrane and soluble forms of the major surface protein of Leishmania promastigotes. J Biol Chem. 1985 Dec 15;260(29):15504–15509. [PubMed] [Google Scholar]
  5. Bray R. S. Leishmania mexicana mexicana: attachment and uptake of promastigotes to and by macrophages in vitro. J Protozool. 1983 May;30(2):314–322. doi: 10.1111/j.1550-7408.1983.tb02922.x. [DOI] [PubMed] [Google Scholar]
  6. Chang C. S., Chang K. P. Monoclonal antibody affinity purification of a Leishmania membrane glycoprotein and its inhibition of leishmania-macrophage binding. Proc Natl Acad Sci U S A. 1986 Jan;83(1):100–104. doi: 10.1073/pnas.83.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chang C. S., Inserra T. J., Kink J. A., Fong D., Chang K. P. Expression and size heterogeneity of a 63 kilodalton membrane glycoprotein during growth and transformation of Leishmania mexicana amazonensis. Mol Biochem Parasitol. 1986 Feb;18(2):197–210. doi: 10.1016/0166-6851(86)90038-1. [DOI] [PubMed] [Google Scholar]
  8. Chang K. P. Cellular and molecular mechanisms of intracellular symbiosis in leishmaniasis. Int Rev Cytol Suppl. 1983;14:267–305. [PubMed] [Google Scholar]
  9. Chang K. P. Leishmania donovani-macrophage binding mediated by surface glycoproteins/antigens: characterization in vitro by a radioisotopic assay. Mol Biochem Parasitol. 1981 Nov;4(1-2):67–76. doi: 10.1016/0166-6851(81)90030-x. [DOI] [PubMed] [Google Scholar]
  10. Chang K. P. Leishmania donovani: promastigote--macrophage surface interactions in vitro. Exp Parasitol. 1979 Oct;48(2):175–189. doi: 10.1016/0014-4894(79)90097-3. [DOI] [PubMed] [Google Scholar]
  11. Channon J. Y., Roberts M. B., Blackwell J. M. A study of the differential respiratory burst activity elicited by promastigotes and amastigotes of Leishmania donovani in murine resident peritoneal macrophages. Immunology. 1984 Oct;53(2):345–355. [PMC free article] [PubMed] [Google Scholar]
  12. Etges R. J., Bouvier J., Hoffman R., Bordier C. Evidence that the major surface proteins of three Leishmania species are structurally related. Mol Biochem Parasitol. 1985 Feb;14(2):141–149. doi: 10.1016/0166-6851(85)90033-7. [DOI] [PubMed] [Google Scholar]
  13. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  14. Griffin F. M., Jr, Mullinax P. J. In vivo activation of macrophage C3 receptors for phagocytosis. J Exp Med. 1985 Jul 1;162(1):352–357. doi: 10.1084/jem.162.1.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Handman E., Goding J. W. The Leishmania receptor for macrophages is a lipid-containing glycoconjugate. EMBO J. 1985 Feb;4(2):329–336. doi: 10.1002/j.1460-2075.1985.tb03633.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jung C. Y., Rampal A. L. Cytochalasin B binding sites and glucose transport carrier in human erythrocyte ghosts. J Biol Chem. 1977 Aug 10;252(15):5456–5463. [PubMed] [Google Scholar]
  17. Klempner M. S., Cendron M., Wyler D. J. Attachment of plasma membrane vesicles of human macrophages to Leishmania tropica promastigotes. J Infect Dis. 1983 Sep;148(3):377–384. doi: 10.1093/infdis/148.3.377. [DOI] [PubMed] [Google Scholar]
  18. Konish M., Shepherd V., Holt G., Stahl P. Uptake of glycoproteins and glycoconjugates by macrophages. Methods Enzymol. 1983;98:301–304. doi: 10.1016/0076-6879(83)98157-0. [DOI] [PubMed] [Google Scholar]
  19. Kweider M., Lemesre J. L., Darcy F., Kusnierz J. P., Capron A., Santoro F. Infectivity of Leishmania braziliensis promastigotes is dependent on the increasing expression of a 65,000-dalton surface antigen. J Immunol. 1987 Jan 1;138(1):299–305. [PubMed] [Google Scholar]
  20. Lepay D. A., Nogueira N., Cohn Z. Surface antigens of Leishmania donovani promastigotes. J Exp Med. 1983 May 1;157(5):1562–1572. doi: 10.1084/jem.157.5.1562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Marsden P. D. Selective primary health care: strategies for control of disease in the developing world. XIV. Leishmaniasis. Rev Infect Dis. 1984 Sep-Oct;6(5):736–744. doi: 10.1093/clinids/6.5.736. [DOI] [PubMed] [Google Scholar]
  22. Michl J., Pieczonka M. M., Unkeless J. C., Silverstein S. C. Effects of immobilized immune complexes on Fc- and complement-receptor function in resident and thioglycollate-elicited mouse peritoneal macrophages. J Exp Med. 1979 Sep 19;150(3):607–621. doi: 10.1084/jem.150.3.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mosser D. M., Edelson P. J. Activation of the alternative complement pathway by Leishmania promastigotes: parasite lysis and attachment to macrophages. J Immunol. 1984 Mar;132(3):1501–1505. [PubMed] [Google Scholar]
  24. Mosser D. M., Edelson P. J. The mouse macrophage receptor for C3bi (CR3) is a major mechanism in the phagocytosis of Leishmania promastigotes. J Immunol. 1985 Oct;135(4):2785–2789. [PubMed] [Google Scholar]
  25. Mosser D. M., Vlassara H., Edelson P. J., Cerami A. Leishmania promastigotes are recognized by the macrophage receptor for advanced glycosylation endproducts. J Exp Med. 1987 Jan 1;165(1):140–145. doi: 10.1084/jem.165.1.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Murray H. W., Cartelli D. M. Killing of intracellular Leishmania donovani by human mononuclear phagocytes. Evidence for oxygen-dependent and -independent leishmanicidal activity. J Clin Invest. 1983 Jul;72(1):32–44. doi: 10.1172/JCI110972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pearson R. D., Harcus J. L., Symes P. H., Romito R., Donowitz G. R. Failure of the phagocytic oxidative response to protect human monocyte-derived macrophages from infection by Leishmania donovani. J Immunol. 1982 Sep;129(3):1282–1286. [PubMed] [Google Scholar]
  28. Pearson R. D., Steigbigel R. T. Mechanism of lethal effect of human serum upon Leishmania donovani. J Immunol. 1980 Nov;125(5):2195–2201. [PubMed] [Google Scholar]
  29. Pearson R. D., Steigbigel R. T. Phagocytosis and killing of the protozoan Leishmania donovani by human polymorphonuclear leukocytes. J Immunol. 1981 Oct;127(4):1438–1443. [PubMed] [Google Scholar]
  30. Pearson R. D., Sullivan J. A., Roberts D., Romito R., Mandell G. L. Interaction of Leishmania donovani promastigotes with human phagocytes. Infect Immun. 1983 Apr;40(1):411–416. doi: 10.1128/iai.40.1.411-416.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pearson R. D., Wheeler D. A., Harrison L. H., Kay H. D. The immunobiology of leishmaniasis. Rev Infect Dis. 1983 Sep-Oct;5(5):907–927. doi: 10.1093/clinids/5.5.907. [DOI] [PubMed] [Google Scholar]
  32. Ross G. D., Cain J. A., Lachmann P. J. Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J Immunol. 1985 May;134(5):3307–3315. [PubMed] [Google Scholar]
  33. Ross G. D., Medof M. E. Membrane complement receptors specific for bound fragments of C3. Adv Immunol. 1985;37:217–267. doi: 10.1016/s0065-2776(08)60341-7. [DOI] [PubMed] [Google Scholar]
  34. Russell D. G., Wilhelm H. The involvement of the major surface glycoprotein (gp63) of Leishmania promastigotes in attachment to macrophages. J Immunol. 1986 Apr 1;136(7):2613–2620. [PubMed] [Google Scholar]
  35. Sacks D. L., Hieny S., Sher A. Identification of cell surface carbohydrate and antigenic changes between noninfective and infective developmental stages of Leishmania major promastigotes. J Immunol. 1985 Jul;135(1):564–569. [PubMed] [Google Scholar]
  36. Sacks D. L., Perkins P. V. Identification of an infective stage of Leishmania promastigotes. Science. 1984 Mar 30;223(4643):1417–1419. doi: 10.1126/science.6701528. [DOI] [PubMed] [Google Scholar]
  37. Stahl P. D., Rodman J. S., Miller M. J., Schlesinger P. H. Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1399–1403. doi: 10.1073/pnas.75.3.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Stahl P., Gordon S. Expression of a mannosyl-fucosyl receptor for endocytosis on cultured primary macrophages and their hybrids. J Cell Biol. 1982 Apr;93(1):49–56. doi: 10.1083/jcb.93.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stahl P., Schlesinger P. H., Sigardson E., Rodman J. S., Lee Y. C. Receptor-mediated pinocytosis of mannose glycoconjugates by macrophages: characterization and evidence for receptor recycling. Cell. 1980 Jan;19(1):207–215. doi: 10.1016/0092-8674(80)90402-x. [DOI] [PubMed] [Google Scholar]
  40. Sung S. S., Nelson R. S., Silverstein S. C. Yeast mannans inhibit binding and phagocytosis of zymosan by mouse peritoneal macrophages. J Cell Biol. 1983 Jan;96(1):160–166. doi: 10.1083/jcb.96.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Todd R. F., 3rd, Griffin J. D., Ritz J., Nadler L. M., Abrams T., Schlossman S. F. Expression of normal monocyte-macrophage differentiation antigens on HL60 promyelocytes undergoing differentiation induced by leukocyte-conditioned medium or phorbol diester. Leuk Res. 1981;5(6):491–495. doi: 10.1016/0145-2126(81)90119-3. [DOI] [PubMed] [Google Scholar]
  42. Todd R. F., 3rd, Nadler L. M., Schlossman S. F. Antigens on human monocytes identified by monoclonal antibodies. J Immunol. 1981 Apr;126(4):1435–1442. [PubMed] [Google Scholar]
  43. Wilson M. E., Innes D. J., Sousa A. D., Pearson R. D. Early histopathology of experimental infection with Leishmania donovani in hamsters. J Parasitol. 1987 Feb;73(1):55–63. [PubMed] [Google Scholar]
  44. Wilson M. E., Pearson R. D. Evidence that Leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism. J Immunol. 1986 Jun 15;136(12):4681–4688. [PubMed] [Google Scholar]
  45. Wilson M. E., Pearson R. D. Stage-specific variations in lectin binding to Leishmania donovani. Infect Immun. 1984 Oct;46(1):128–134. doi: 10.1128/iai.46.1.128-134.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wozencraft A. O., Sayers G., Blackwell J. M. Macrophage type 3 complement receptors mediate serum-independent binding of Leishmania donovani. Detection of macrophage-derived complement on the parasite surface by immunoelectron microscopy. J Exp Med. 1986 Oct 1;164(4):1332–1337. doi: 10.1084/jem.164.4.1332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wright S. D., Griffin F. M., Jr Activation of phagocytic cells' C3 receptors for phagocytosis. J Leukoc Biol. 1985 Aug;38(2):327–339. doi: 10.1002/jlb.38.2.327. [DOI] [PubMed] [Google Scholar]
  48. Wright S. D., Licht M. R., Craigmyle L. S., Silverstein S. C. Communication between receptors for different ligands on a single cell: ligation of fibronectin receptors induces a reversible alteration in the function of complement receptors on cultured human monocytes. J Cell Biol. 1984 Jul;99(1 Pt 1):336–339. doi: 10.1083/jcb.99.1.336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. Wright S. D., Silverstein S. C. Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J Exp Med. 1983 Dec 1;158(6):2016–2023. doi: 10.1084/jem.158.6.2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Wyler D. J. In vitro parasite-monocyte interactions in human leishmaniasis. Evidence for an active role of the parasite in attachment. J Clin Invest. 1982 Jul;70(1):82–88. doi: 10.1172/JCI110606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Wyler D. J., Sypek J. P., McDonald J. A. In vitro parasite-monocyte interactions in human leishmaniasis: possible role of fibronectin in parasite attachment. Infect Immun. 1985 Aug;49(2):305–311. doi: 10.1128/iai.49.2.305-311.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Zenian A. Leishmania tropica: biochemical aspects of promastigotes' attachment to macrophages in vitro. Exp Parasitol. 1981 Apr;51(2):175–187. doi: 10.1016/0014-4894(81)90106-5. [DOI] [PubMed] [Google Scholar]

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