STAGE-SPECIFIC GLYCOSPHINGOLIPIDS FROM AMASTIGOTE FORMS OF LEISHMANIA (L) AMAZONENSIS - IMMUNOGENICITY AND ROLE IN PARASITE BINDING AND INVASION OF MACROPHAGES
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1993-06-25
Autores
Straus, Anita Hilda [UNIFESP]
Levery, S. B.
Jasiulionis, Miriam Galvonas [UNIFESP]
Salyan, MEK
Steele, S. J.
Travassos, Luiz Rodolpho [UNIFESP]
Hakomori, S. I.
Takahashi, Helio Kiyoshi [UNIFESP]
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Neutral glycosphingolipids (GSLs) from amastigote forms of Leishmania (L.) amazonensis were isolated, and their structures and biological properties were characterized. Based on various immunochemical methods, these GSLs were shown to be expressed at certain stages of amastigote development. GSLs were extracted and purified from amastigotes of hamster foot lesions by established procedures. Three mouse monoclonal antibodies (MoAbs) specific for carbohydrate epitopes of these GSLs were established, and their inhibition of parasite binding and macrophage invasion was analyzed. MoAb ST-3 inhibited 80% of macrophage invasion by amastigotes and 60% of that by promastigotes. Since GSLs reacting with MoAb ST-3 were found in amastigotes but not in promastigotes, ST-3 reactivity with promastigotes presumably depends on an epitope present on an unidentified promastigote glycoconjugate. MoAbs ST-4 and ST-5 inhibited 60-80% of macrophage invasion by amastigotes but were not effective in preventing macrophage invasion by promastigotes. Fab fragments of ST-3 inhibited invasion of cultured mouse macrophages by amastigotes (80%) or promastigotes (60%). The GSL with the simplest structure recognized by these MoAbs was isolated and characterized (by negative ion fast atom bombardment-mass spectrometry, gas chromatography-mass spectrometry of the permethylated compound, degradation with exoglycosidases, and H-1 NMR) as the novel globoseries structure Galbeta1 --> 3Galalpha1-->4Galbeta1-->4Glcbeta1-->Cer, which has beta1-->3Gal in place of the beta1-->3GalNAc of globoside. The ceramide contains a 16:0 fatty acid and d18:1 sphingosine as the long chain base. The MoAbs also reacted with a series of GSLs from amastigote forms of L. amazonensis, with longer carbohydrate chains, probably containing identical end groups Galbeta1-->3Galalpha1-->R. Expression of surface GSLs may render amastigote forms more effective than promastigotes in binding and invading host macrophages, thus enhancing the infectious process.
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Journal Of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 268, n. 18, p. 13723-13730, 1993.