Abstract

Lipophosphoglycan (LPG) was isolated from the culture supernatant of Leishmania mexicana promastigotes and its structure elucidated by a combination of 1H NMR, fast atom bombardment mass spectrometry, methylation analysis, and chemical and enzymatic modifications. It consists of the repeating phosphorylated oligosaccharides PO4-6Gal beta 1-4Man alpha 1- and PO4-6[Glc beta 1-3]Gal beta 1-4Man alpha 1-, which are linked together in linear chains by phosphodiester linkages. Each chain of repeat units is linked to a phosphosaccharide core with the structure PO4-6Gal alpha 1-6Gal alpha 1-3Galf beta 1- 3[Glc alpha 1-PO4-6]Man alpha 1-3Man alpha 1-4GlcNH2 alpha 1-6 myo-inositol, where the myo-inositol residue forms the head group of a lyso-alkylphosphatidylinositol moiety. The nonreducing terminus of the repeat chains appear to be capped with the neutral oligosaccharides Man alpha 1-2Man, Man alpha 1-2Man alpha 1-2Man, or Man alpha 1-2[Gal beta 1-4]Man. Cellular LPG, isolated from promastigotes, has a very similar structure to the culture supernatant LPG. However, it differs from culture supernatant LPG in the average number of phosphorylated oligosaccharide repeat units (20 versus 28) and in alkyl chain composition. Although culture supernatant LPG contained predominantly C24:0 alkyl chains, cellular LPG contained approximately equal amounts of C24:0 and C26:0 alkyl chains. It is suggested that culture supernatant LPG is passively shed from promastigotes and that it may contribute significantly, but not exclusively, to the "excreted factor" used for serotyping Leishmania spp. Comparison of L. mexicana LPG with the LPGs of Leishmania major and Leishmania donovani indicate that these molecules are highly conserved but that species-specific differences occur in the phosphorylated oligosaccharide repeat branches and in the relative abundance of the neutral cap structures.

Highlights

  • Lipophosphoglycan (LPG) was isolated fromthe cul- Protozoa of the genus Leishmania cause a spectrum of ture supernatant of Leishmania mexicana promasti- diseases in the tropics, subtropics, and Mediterranean regions

  • LPG is the major cell surface glycoconvery similar structure to the culture supernLatPaGnt. It differs from culture supernatant LPG in the average numberof phosphorylated oligosaccharide repeat units (20uersus 28) and in alkyl chaincomposition

  • Considering the possible mechanism of LPG release from the promastigote surface, a complex set of equilibria involving LPG monomers and micelles, LPG-serum albumin complexes (King et al, 1987), and the lipid bilayer of the parasite plasma membrane must be taken into account

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Summary

Introduction

Lipophosphoglycan (LPG) was isolated fromthe cul- Protozoa of the genus Leishmania cause a spectrum of ture supernatant of Leishmania mexicana promasti- diseases in the tropics, subtropics, and Mediterranean regions. Manal-S[Ga~l-4]Man. lipophosphoglycan (LPG) (reviewed by Turco (1990) and Cellular LPG, isolated from promastigotes, has a McConville (1991)).

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