Surface antigens of Leishmania mexicana amastigotes: characterization of glycoinositol phospholipids and a macrophage-derived glycosphingolipid.
Amastigotes of the protozoan parasite Leishmania proliferate in phagolysosomes of macrophages. They abundantly express glycoinositol phospholipids (GIPLs), which are considered necessary for parasite survival by providing a shield at the surface against lysosomal hydrolases and by serving as receptors for the interaction with host cells. The structures of four GIPLs of L. mexicana amastigotes were characterized by a combination of gas-liquid chromatography-mass spectrometry, methylation linkage analysis and enzymatic treatments. They contain the glycan structures Man alpha 1-3Man alpha 1-4GlcN (iM2), Man alpha 1-6(Man alpha 1-3)Man alpha 1-4GlcN (iM3), Man alpha 1-2Man alpha 1-6(Man alpha 1-3)-Man alpha 1-4GlcN (iM4) and (NH2-CH2CH2-PO4)Man alpha 1-6(Man alpha 1-3)Man alpha 1-4GlcN (EPiM3), which are linked to alkylacyl-phosphatidylinositol. The predominant amastigote GIPL, EPiM3 (approximately 2 x 10(7) molecules/cell), is located at the parasite cell surface, in the flagellar pocket and in lysosomal membranes, but not on host cell structures as shown by immunofluorescence and immunoelectron microscopy. In addition, amastigotes in infected Balb/c mice contain a glycolipid with similar distribution as EPiM3, which has the same characteristics as the Forssman antigen of mammalian cells. In contrast to EPiM3, there is strong evidence that this glycosphingolipid is not synthesized by amastigotes but by macrophages in the lesion. This suggests a mechanism of lipid transfer from the macrophage to the parasite.
Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Tübingen, Federal Republic of Germany.
G
G
Winter
M
M
Fuchs
M J
MJ
McConville
Y D
YD
Stierhof
P
P
Overath
D000818:Animals; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D002240:Carbohydrate Sequence; D005577:Forssman Antigen / Q000276:immunology* / Q000378:metabolism; D006017:Glycolipids / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D006028:Glycosphingolipids / Q000276:immunology* / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000276:immunology*; D007894:Leishmania mexicana / Q000254:growth & development / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010743:Phospholipids / Q000276:immunology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D006017:Glycolipids; D006028:Glycosphingolipids; D017261:Glycosylphosphatidylinositols; D010743:Phospholipids; D005577:Forssman Antigen; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase