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. 1991 Jul 15;277(Pt 2):451–456. doi: 10.1042/bj2770451

Down-regulation of mannose receptors on macrophages after infection with Leishmania donovani.

N Basu 1, R Sett 1, P K Das 1
PMCID: PMC1151255  PMID: 1859373

Abstract

Macrophages express a mannose-specific endocytosis receptor that binds and internalizes mannose-terminated glycoproteins. Infection of mouse peritoneal macrophages with Leishmania donovani resulted in a decrease in mannose-receptor activity. With 125I-labelled beta-glucuronidase as ligand, a 2-fold decrease in uptake rate was observed in infected cells, with no change in Kuptake. Cell-surface binding of 125I-mannose-BSA was diminished 2.5-fold after infection. The decrease in ligand binding appeared to be due to a decrease in the number of sites, with no change in affinity. Elimination of parasites from infected cells by treatment with neoglycoprotein-conjugated methotrexate resulted in an increase in receptor number. Cycloheximide suppressed the drug-treatment-mediated rise in receptor number in infected macrophages. A decrease in receptor activity was also observed in liver Kupffer cells isolated from parasite-infected mice. Binding of ligand by another carbohydrate receptor, the mannose 6-phosphate receptor, was not altered by infection. Phagocytosis of yeast cells was also not altered. These results suggest that mannose receptor synthesis in macrophages is specifically suppressed after infection with Leishmania parasites.

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Selected References

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  1. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bozeman P. M., Hoidal J. R., Shepherd V. L. Oxidant-mediated inhibition of ligand uptake by the macrophage mannose receptor. J Biol Chem. 1988 Jan 25;263(3):1240–1247. [PubMed] [Google Scholar]
  3. Chakraborty P., Bhaduri A. N., Das P. K. Neoglycoproteins as carriers for receptor-mediated drug targeting in the treatment of experimental visceral leishmaniasis. J Protozool. 1990 Sep-Oct;37(5):358–364. doi: 10.1111/j.1550-7408.1990.tb01158.x. [DOI] [PubMed] [Google Scholar]
  4. Chakraborty P., Bhaduri A. N., Das P. K. Sugar receptor mediated drug delivery to macrophages in the therapy of experimental visceral leishmaniasis. Biochem Biophys Res Commun. 1990 Jan 15;166(1):404–410. doi: 10.1016/0006-291x(90)91959-v. [DOI] [PubMed] [Google Scholar]
  5. Chakraborty P., Das P. K. Suppression of macrophage lysosomal enzymes after Leishmania donovani infection. Biochem Med Metab Biol. 1989 Feb;41(1):46–55. doi: 10.1016/0885-4505(89)90007-8. [DOI] [PubMed] [Google Scholar]
  6. Chang K. P., Dwyer D. M. Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro. Science. 1976 Aug 20;193(4254):678–680. doi: 10.1126/science.948742. [DOI] [PubMed] [Google Scholar]
  7. Chung K. N., Shepherd V. L., Stahl P. D. Swainsonine and castanospermine blockade of mannose glycoprotein uptake by macrophages. Apparent inhibition of receptor-mediated endocytosis by endogenous ligands. J Biol Chem. 1984 Dec 10;259(23):14637–14641. [PubMed] [Google Scholar]
  8. Clohisy D. R., Bar-Shavit Z., Chappel J. C., Teitelbaum S. L. 1,25-Dihydroxyvitamin D3 modulates bone marrow macrophage precursor proliferation and differentiation. Up-regulation of the mannose receptor. J Biol Chem. 1987 Nov 25;262(33):15922–15929. [PubMed] [Google Scholar]
  9. Das P. K., Ghosh P., Bachhawat B. K., Das M. K. Liposomes as carrier for production of sugar specific antibodies: preparation of antigalactosyl antiserum. Immunol Commun. 1982;11(1):17–24. doi: 10.3109/08820138209050720. [DOI] [PubMed] [Google Scholar]
  10. Das P. K., Murray G. J., Barranger J. A. Studies on the turnover of glucocerebrosidase in cultured rat peritoneal macrophages and normal human fibroblasts. Eur J Biochem. 1986 Jan 15;154(2):445–450. doi: 10.1111/j.1432-1033.1986.tb09417.x. [DOI] [PubMed] [Google Scholar]
  11. Dijkstra J., van Galen W. J., Hulstaert C. E., Kalicharan D., Roerdink F. H., Scherphof G. L. Interaction of liposomes with Kupffer cells in vitro. Exp Cell Res. 1984 Jan;150(1):161–176. doi: 10.1016/0014-4827(84)90711-0. [DOI] [PubMed] [Google Scholar]
  12. Diment S., Stahl P. Macrophage endosomes contain proteases which degrade endocytosed protein ligands. J Biol Chem. 1985 Dec 5;260(28):15311–15317. [PubMed] [Google Scholar]
  13. Ezekowitz R. A., Austyn J., Stahl P. D., Gordon S. Surface properties of bacillus Calmette-Guérin-activated mouse macrophages. Reduced expression of mannose-specific endocytosis, Fc receptors, and antigen F4/80 accompanies induction of Ia. J Exp Med. 1981 Jul 1;154(1):60–76. doi: 10.1084/jem.154.1.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ezekowitz R. A. The role of growth factors and interferons in the induction of activated murine macrophages from bone marrow precursors. Immunol Lett. 1985;11(3-4):135–140. doi: 10.1016/0165-2478(85)90159-2. [DOI] [PubMed] [Google Scholar]
  15. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Geuze H. J., Slot J. W., Strous G. J., Lodish H. F., Schwartz A. L. Intracellular site of asialoglycoprotein receptor-ligand uncoupling: double-label immunoelectron microscopy during receptor-mediated endocytosis. Cell. 1983 Jan;32(1):277–287. doi: 10.1016/0092-8674(83)90518-4. [DOI] [PubMed] [Google Scholar]
  17. Ghosh A. K., Bhattacharyya F. K., Ghosh D. K. Leishmania donovani: amastigote inhibition and mode of action of berberine. Exp Parasitol. 1985 Dec;60(3):404–413. doi: 10.1016/0014-4894(85)90047-5. [DOI] [PubMed] [Google Scholar]
  18. Imber M. J., Pizzo S. V., Johnson W. J., Adams D. O. Selective diminution of the binding of mannose by murine macrophages in the late stages of activation. J Biol Chem. 1982 May 10;257(9):5129–5135. [PubMed] [Google Scholar]
  19. Kaminski N. E., Roberts J. F., Guthrie F. E. A rapid spectrophotometric method for assessing macrophage phagocytic activity. Immunol Lett. 1985;10(6):329–331. doi: 10.1016/0165-2478(85)90127-0. [DOI] [PubMed] [Google Scholar]
  20. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  21. Munthe-Kaas A. C., Seglen P. O. The use of Metrizamide as a gradient medium for isopycnic separation of rat liver cells. FEBS Lett. 1974 Aug 1;43(3):252–256. doi: 10.1016/0014-5793(74)80654-x. [DOI] [PubMed] [Google Scholar]
  22. Murray G. J. Lectin-specific targeting of lysosomal enzymes to reticuloendothelial cells. Methods Enzymol. 1987;149:25–42. doi: 10.1016/0076-6879(87)49041-1. [DOI] [PubMed] [Google Scholar]
  23. Rabinovitch M., Topper G., Cristello P., Rich A. Receptor-mediated entry of peroxidases into the parasitophorous vacuoles of macrophages infected with Leishmania Mexicana amazonensis. J Leukoc Biol. 1985 Mar;37(3):247–261. doi: 10.1002/jlb.37.3.247. [DOI] [PubMed] [Google Scholar]
  24. Shepherd V. L., Campbell E. J., Senior R. M., Stahl P. D. Characterization of the mannose/fucose receptor on human mononuclear phagocytes. J Reticuloendothel Soc. 1982 Dec;32(6):423–431. [PubMed] [Google Scholar]
  25. Shepherd V. L., Freeze H. H., Miller A. L., Stahl P. D. Identification of mannose 6-phosphate receptors in rabbit alveolar macrophages. J Biol Chem. 1984 Feb 25;259(4):2257–2261. [PubMed] [Google Scholar]
  26. Shepherd V. L., Konish M. G., Stahl P. Dexamethasone increases expression of mannose receptors and decreases extracellular lysosomal enzyme accumulation in macrophages. J Biol Chem. 1985 Jan 10;260(1):160–164. [PubMed] [Google Scholar]
  27. Shepherd V. L., Stahl P. D., Bernd P., Rabinovitch M. Receptor-mediated entry of beta-glucuronidase into the parasitophorous vacuoles of macrophages infected with Leishmania mexicana amazonensis. J Exp Med. 1983 May 1;157(5):1471–1482. doi: 10.1084/jem.157.5.1471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Wileman T., Boshans R., Stahl P. Uptake and transport of mannosylated ligands by alveolar macrophages. Studies on ATP-dependent receptor-ligand dissociation. J Biol Chem. 1985 Jun 25;260(12):7387–7393. [PubMed] [Google Scholar]

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