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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
1986-7-7
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pubmed:abstractText |
The pathogenic protozoan Leishmania donovani must gain entrance into mononuclear phagocytes to successfully parasitize man. The parasite's extra-cellular promastigote stage is ingested by human peripheral blood monocytes or monocyte-derived macrophages in the absence of serum, in a manner characteristic of receptor-mediated endocytosis. We have found remarkable similarities between the macrophage receptor(s) for promastigotes and a previously characterized eucaryotic receptor system, the mannose/fucose receptor (MFR), that mediates the binding of zymosan particles and mannose- or fucose-terminal glycoconjugates to macrophages. Ingestion of promastigotes by monocyte-derived macrophages was inhibited by several MFR ligands. Mannan (2.5 mg/ml) decreased ingestion by 63.7% (p less than 0.001), and the neoglycoproteins mannose-BSA and fucose-BSA (20 micrograms/ml) inhibited parasite ingestion by 46.5% and 39.6%, respectively (p less than 0.04). In contrast, promastigote ingestion by monocytes was unaffected by MFR ligands. These results are consistent with reports that MFR activity is present in monocyte-derived macrophages but not in monocytes. Furthermore, attachment of promastigotes to macrophages, assessed by using cytochalasin D to prevent phagocytosis, was reduced 49.8% by mannan. Reorientation of the MFR to the ventral surface of the cell was achieved by plating macrophages onto mannan-coated coverslips, reducing MFR activity on the exposed cell surface by 94% as assessed by binding of 125I-mannose-BSA. Under these conditions, ingestion of promastigotes was inhibited by 71.4% (p less than 0.006). Internalization of the MFR by exposure of macrophages to zymosan before infection with promastigotes resulted in a 62.3% decrease in parasite ingestion (p less than 0.006). Additionally NH4Cl, a weak lysosomotropic base that impairs MFR recycling, decreased macrophage ingestion of promastigotes by 38.2% (p less than 0.03, 30 mM NH4Cl). Subinhibitory concentrations of NH4Cl (10 mM) and of mannan (0.25 mg/ml) together inhibited parasite ingestion by 76.4% (p less than 0.002). These studies suggest that L. donovani promastigotes may utilize a receptor system on human monocyte-derived macrophages, the MFR, to efficiently parasitize the human host.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ammonium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins, C-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Mannans,
http://linkedlifedata.com/resource/pubmed/chemical/Mannose,
http://linkedlifedata.com/resource/pubmed/chemical/Mannose-Binding Lectins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Albumin,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Albumin, Bovine,
http://linkedlifedata.com/resource/pubmed/chemical/Trypsin,
http://linkedlifedata.com/resource/pubmed/chemical/mannose receptor,
http://linkedlifedata.com/resource/pubmed/chemical/mannose-bovine serum albumin...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
136
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4681-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:3711662-Adult,
pubmed-meshheading:3711662-Ammonium Chloride,
pubmed-meshheading:3711662-Animals,
pubmed-meshheading:3711662-Endocytosis,
pubmed-meshheading:3711662-Humans,
pubmed-meshheading:3711662-Lectins, C-Type,
pubmed-meshheading:3711662-Leishmania donovani,
pubmed-meshheading:3711662-Lysosomes,
pubmed-meshheading:3711662-Mannans,
pubmed-meshheading:3711662-Mannose,
pubmed-meshheading:3711662-Mannose-Binding Lectins,
pubmed-meshheading:3711662-Monocytes,
pubmed-meshheading:3711662-Phagocytosis,
pubmed-meshheading:3711662-Receptors, Cell Surface,
pubmed-meshheading:3711662-Receptors, Immunologic,
pubmed-meshheading:3711662-Serum Albumin,
pubmed-meshheading:3711662-Serum Albumin, Bovine,
pubmed-meshheading:3711662-Trypsin
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pubmed:year |
1986
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pubmed:articleTitle |
Evidence that Leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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