Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Mar 1;167(3):887–902. doi: 10.1084/jem.167.3.887

Complement binding by two developmental stages of Leishmania major promastigotes varying in expression of a surface lipophosphoglycan

PMCID: PMC2188887  PMID: 3280727

Abstract

The binding of complement by two developmentally distinct stages of Leishmania major has been studied. Noninfective log phase growth (LOG) promastigotes (serum sensitive) activate complement with deposition of covalently bound C3b onto the surface of the parasite. Infective, peanut agglutinin (PNA-) metacyclic stage promastigotes (serum resistant) also bear mainly C3b after incubation in serum, but a major portion of deposited C3 is present as a 110 X 10(3) mol wt C3 fragment. Whereas deposition of C3b on LOG promastigotes is mediated through the alternative pathway. PNA- parasites are unable to activate the alternative pathway in nonimmune serum. C3 is released from the parasite surface by proteolytic cleavage, at a rate which is nearly threefold greater for LOG than for PNA- promastigotes. Immunoprecipitation experiments show that the developmentally regulated lipophosphoglycan is a major C3 acceptor on both LOG and PNA- parasites. These experiments, which are the first to compare the form and processing of complement on infective and noninfective promastigotes of Leishmania, provide a framework for further definition of the differential C3 receptor-dependent uptake and survival of these parasites within mononuclear phagocytes.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. 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]
  2. Etges R., Bouvier J., Bordier C. The major surface protein of Leishmania promastigotes is a protease. J Biol Chem. 1986 Jul 15;261(20):9098–9101. [PubMed] [Google Scholar]
  3. Fearon D. T. Regulation by membrane sialic acid of beta1H-dependent decay-dissociation of amplification C3 convertase of the alternative complement pathway. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1971–1975. doi: 10.1073/pnas.75.4.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ferrante A., Allison A. C. Alternative pathway activation of complement by African trypanosomes lacking a glycoprotein coat. Parasite Immunol. 1983 Sep;5(5):491–498. doi: 10.1111/j.1365-3024.1983.tb00763.x. [DOI] [PubMed] [Google Scholar]
  5. Franke E. D., McGreevy P. B., Katz S. P., Sacks D. L. Growth cycle-dependent generation of complement-resistant Leishmania promastigotes. J Immunol. 1985 Apr;134(4):2713–2718. [PubMed] [Google Scholar]
  6. 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]
  7. Gardiner P. R., Dwyer D. M. Radioiodination and identification of externally disposed membrane components of Leishmania tropica. Mol Biochem Parasitol. 1983 Aug;8(4):283–295. doi: 10.1016/0166-6851(83)90075-0. [DOI] [PubMed] [Google Scholar]
  8. Giannini M. S. Effects of promastigote growth phase, frequency of subculture, and host age on promastigote-initiated infections with Leishmania donovani in the golden hamster. J Protozool. 1974 Oct;21(4):521–527. doi: 10.1111/j.1550-7408.1974.tb03692.x. [DOI] [PubMed] [Google Scholar]
  9. Hammer C. H., Wirtz G. H., Renfer L., Gresham H. D., Tack B. F. Large scale isolation of functionally active components of the human complement system. J Biol Chem. 1981 Apr 25;256(8):3995–4006. [PubMed] [Google Scholar]
  10. 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]
  11. Handman E., Greenblatt C. L., Goding J. W. An amphipathic sulphated glycoconjugate of Leishmania: characterization with monoclonal antibodies. EMBO J. 1984 Oct;3(10):2301–2306. doi: 10.1002/j.1460-2075.1984.tb02130.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Handman E., Mitchell G. F. Immunization with Leishmania receptor for macrophages protects mice against cutaneous leishmaniasis. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5910–5914. doi: 10.1073/pnas.82.17.5910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Joiner K. A., Hammer C. H., Brown E. J., Cole R. J., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. I. Terminal complement components are deposited and released from Salmonella minnesota S218 without causing bacterial death. J Exp Med. 1982 Mar 1;155(3):797–808. doi: 10.1084/jem.155.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Lambris J. D., Müller-Eberhard H. J. The multifunctional role of C3: structural analysis of its interactions with physiological ligands. Mol Immunol. 1986 Nov;23(11):1237–1242. doi: 10.1016/0161-5890(86)90157-4. [DOI] [PubMed] [Google Scholar]
  16. Mosser D. M., Burke S. K., Coutavas E. E., Wedgwood J. F., Edelson P. J. Leishmania species: mechanisms of complement activation by five strains of promastigotes. Exp Parasitol. 1986 Dec;62(3):394–404. doi: 10.1016/0014-4894(86)90048-2. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Mosser D. M., Edelson P. J. The third component of complement (C3) is responsible for the intracellular survival of Leishmania major. 1987 May 28-Jun 3Nature. 327(6120):329–331. doi: 10.1038/327329b0. [DOI] [PubMed] [Google Scholar]
  20. Nogueira N., Bianco C., Cohn Z. Studies on the selective lysis and purification of Trypanosoma cruzi. J Exp Med. 1975 Jul 1;142(1):224–229. doi: 10.1084/jem.142.1.224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Rizvi F. S., Afchain D., Sherlock I., Sadigursky M., Capron A., Santoro F. Infectivity of Leishmania promastigotes is associated with surface antigenic expression. Immunol Lett. 1985;11(5-6):317–323. doi: 10.1016/0165-2478(85)90114-2. [DOI] [PubMed] [Google Scholar]
  23. Rudzinska M. A. Ultrastructure of intraerythrocytic Babesia microti with emphasis on the feeding mechanism. J Protozool. 1976 May;23(2):224–233. doi: 10.1111/j.1550-7408.1976.tb03759.x. [DOI] [PubMed] [Google Scholar]
  24. Russell D. G. The macrophage-attachment glycoprotein gp63 is the predominant C3-acceptor site on Leishmania mexicana promastigotes. Eur J Biochem. 1987 Apr 1;164(1):213–221. doi: 10.1111/j.1432-1033.1987.tb11013.x. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Sacks D. L., da Silva R. P. The generation of infective stage Leishmania major promastigotes is associated with the cell-surface expression and release of a developmentally regulated glycolipid. J Immunol. 1987 Nov 1;139(9):3099–3106. [PubMed] [Google Scholar]
  28. Turco S. J., Wilkerson M. A., Clawson D. R. Expression of an unusual acidic glycoconjugate in Leishmania donovani. J Biol Chem. 1984 Mar 25;259(6):3883–3889. [PubMed] [Google Scholar]
  29. Venkatesh Y. P., Minich T. M., Law S. K., Levine R. P. Natural release of covalently bound C3b from cell surfaces and the study of this phenomenon in the fluid-phase system. J Immunol. 1984 Mar;132(3):1435–1439. [PubMed] [Google Scholar]
  30. Wozencraft A. O., Blackwell J. M. Increased infectivity of stationary-phase promastigotes of Leishmania donovani: correlation with enhanced C3 binding capacity and CR3-mediated attachment to host macrophages. Immunology. 1987 Apr;60(4):559–563. [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES