Leishmania major proteophosphoglycan is expressed by amastigotes and has an immunomodulatory effect on macrophage function.
Proteophosphoglycan (PPG) is a newly described mucin-like glycoprotein found on the surface of Leishmania major promastigotes and secreted in the culture supernatant. We show here that antigenically similar PPGs are present in several Leishmania species. PPG could also be detected on the surface of amastigotes and in small, parasite-free vesicles in infected macrophages. Because of the similarity of its carbohydrate chains to lipophosphoglycan, a parasite receptor for host macrophages, PPG was tested for binding to macrophages. PPG bound to macrophages and was internalized in a time-dependent manner. PPG inhibited the production of tumor necrosis factor-alpha and synergized with interferon-gamma to stimulate the production of nitric oxide by macrophages. PPG may contribute to the binding of Leishmania to host cells and may play a role in modulating the biology of the infected macrophage at the early stage of infection.
Piani
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The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia.
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Elefanty
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Curtis
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Handman
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D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D004357:Drug Synergism; D004705:Endocytosis; D005455:Fluorescent Antibody Technique; D006028:Glycosphingolipids / Q000737:chemistry; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D007893:Leishmania donovani / Q000737:chemistry / Q000276:immunology; D018320:Leishmania major / Q000737:chemistry / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism*; D007894:Leishmania mexicana / Q000737:chemistry / Q000276:immunology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000953:Antigens, Protozoan; D006028:Glycosphingolipids; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C400527:Ppg1 protein, Leishmania; D011509:Proteoglycans; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; C008290:lipophosphonoglycan; D009569:Nitric Oxide; D007371:Interferon-gamma