Role of (cid:2) - D -Galactofuranose in Leishmania major Macrophage Invasion

The role of glycosylinositol phospholipid 1 (GIPL-1) of Leishmania ( Leishmania ) major in the interaction of promastigotes and amastigotes with macrophages was analyzed. Monoclonal antibody MEST-1, which recog- nizes glycolipids containing terminal galactofuranose (Galf) residues (E. Suzuki, M. S. Toledo, H. K. Taka-hashi, and A. H. Straus, Glycobiology 7:463-468, 1997), was used to detect GIPL-1 in Leishmania by indirect immunofluorescence and to analyze its role in macrophage infectivity. L. major promastigotes showed intense fluorescence with MEST-1, and GIPL-1 was detected in both amastigote and promastigote forms by high- performance thin-layer chromatography immunostaining by using MEST-1. Delipidation of L. major promastigotes with isopropanol-hexane-water eliminated the MEST-1 reactivity, confirming that only GIPL-1 is recognized in either amastigotes or promastigotes of this species. The biological role of GIPL-1 in the ability of L. major to invade macrophages was studied by using either Fab fragments of MEST-1 or methylglycosides. Preincubation of parasites with Fab fragments reduced macrophage infectivity in about 80% of the promas- tigotes and 30% of the amastigotes. Preincubation of peritoneal macrophages with p -nitrophenyl- (cid:1) -galacto-furanoside (10 mM) led to significant ( (cid:3) 80%) inhibition of promastigote infectivity. These data suggest that a putative new receptor recognizing (cid:1) - D -Galf is associated with L. major macrophage infectivity and that GIPL-1 containing a terminal Galf residue is involved in the L. major -macrophage interaction.

[1]  E. Suzuki,et al.  Inhibition of macrophage invasion by monoclonal antibodies specific to Leishmania (Viannia) braziliensis promastigotes and characterisation of their antigens. , 2001, International journal for parasitology.

[2]  R. Mortara,et al.  Reactivity of MEST-1 (Antigalactofuranose) withTrypanosoma cruzi Glycosylinositol Phosphorylceramides (GIPCs): Immunolocalization of GIPCs in Acidic Vesicles of Epimastigotes , 2001, Clinical Diagnostic Laboratory Immunology.

[3]  K. Toyoshima,et al.  Human Intelectin Is a Novel Soluble Lectin That Recognizes Galactofuranose in Carbohydrate Chains of Bacterial Cell Wall* , 2001, The Journal of Biological Chemistry.

[4]  K. Chang,et al.  Interaction of Leishmania gp63 with Cellular Receptors for Fibronectin , 1999, Infection and Immunity.

[5]  S. Levery,et al.  Structure elucidation of sphingolipids from the mycopathogen Paracoccidioides brasiliensis: an immunodominant beta-galactofuranose residue is carried by a novel glycosylinositol phosphorylceramide antigen. , 1998, Biochemistry.

[6]  E. Suzuki,et al.  A monoclonal antibody directed to terminal residue of beta-galactofuranose of a glycolipid antigen isolated from Paracoccidioides brasiliensis: cross-reactivity with Leishmania major and Trypanosoma cruzi. , 1997, Glycobiology.

[7]  M. Ferguson,et al.  The Lipid Structure of the Glycosylphosphatidylinositol-anchored Mucin-like Sialic Acid Acceptors of Trypanosoma cruzi Changes during Parasite Differentiation from Epimastigotes to Infective Metacyclic Trypomastigote Forms (*) , 1995, The Journal of Biological Chemistry.

[8]  W. Colli,et al.  Galactofuranose-containing glycoconjugates in trypanosomatids. , 1995, Glycobiology.

[9]  E. Suzuki,et al.  Immunochemical characterization of carbohydrate antigens from fungi, protozoa and mammals by monoclonal antibodies directed to glycan epitopes. , 1995, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[10]  E. Suzuki,et al.  Glycolipids from Paracoccidioides brasiliensis. Isolation of a galactofuranose-containing glycolipid reactive with sera of patients with paracoccidioidomycosis. , 1995, Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology.

[11]  M. Ferguson,et al.  Biosynthesis of the glycolipid anchor of lipophosphoglycan and the structurally related glycoinositolphospholipids from Leishmania major. , 1995, The Biochemical journal.

[12]  A. Bacic,et al.  Lipophosphoglycan blocks attachment of Leishmania major amastigotes to macrophages , 1995, Infection and immunity.

[13]  P. Brennan,et al.  Major structural features of the cell wall arabinogalactans of Mycobacterium, Rhodococcus, and Nocardia spp. , 1993, Carbohydrate research.

[14]  M. Ferguson,et al.  Characterization of glycoinositol phospholipids in the amastigote stage of the protozoan parasite Leishmania major. , 1993, The Biochemical journal.

[15]  E. Brown,et al.  Ligand specificity of purified complement receptor type three (CD11b/CD18, alpha m beta 2, Mac-1). Indirect effects of an Arg-Gly-Asp (RGD) sequence. , 1993, Journal of immunology.

[16]  M. Ferguson,et al.  The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes. , 1993, The Biochemical journal.

[17]  S. Hakomori,et al.  Stage-specific glycosphingolipids from amastigote forms of Leishmania (L.) amazonensis. Immunogenicity and role in parasite binding and invasion of macrophages. , 1993, The Journal of biological chemistry.

[18]  M. Belosevic,et al.  Comparison of receptors required for entry of Leishmania major amastigotes into macrophages , 1993, Infection and immunity.

[19]  L. Travassos,et al.  A monoclonal antibody (ST-1) directed to the native heparin chain. , 1992, Analytical biochemistry.

[20]  S. Wright,et al.  Lipophosphoglycan from Leishmania mexicana promastigotes binds to members of the CR3, p150,95 and LFA-1 family of leukocyte integrins. , 1990, Journal of immunology.

[21]  P. Brennan,et al.  Predominant structural features of the cell wall arabinogalactan of Mycobacterium tuberculosis as revealed through characterization of oligoglycosyl alditol fragments by gas chromatography/mass spectrometry and by 1H and 13C NMR analyses. , 1990, The Journal of biological chemistry.

[22]  P. Gorin,et al.  Primary structure of the oligosaccharide chain of lipopeptidophosphoglycan of epimastigote forms of Trypanosoma cruzi. , 1990, The Journal of biological chemistry.

[23]  B. F. Hall,et al.  CR1, the C3b receptor, mediates binding of infective Leishmania major metacyclic promastigotes to human macrophages. , 1989, Journal of immunology.

[24]  J. Blackwell,et al.  Monoclonal antibodies that recognize distinct epitopes of the macrophage type three complement receptor differ in their ability to inhibit binding of Leishmania promastigotes harvested at different phases of their growth cycle. , 1988, Immunology.

[25]  S. Wright,et al.  Complement receptor type 3 (CR3) binds to an Arg-Gly-Asp-containing region of the major surface glycoprotein, gp63, of Leishmania promastigotes , 1988, The Journal of experimental medicine.

[26]  R. Pearson,et al.  Roles of CR3 and mannose receptors in the attachment and ingestion of Leishmania donovani by human mononuclear phagocytes , 1988, Infection and immunity.

[27]  A. Cerami,et al.  Leishmania promastigotes are recognized by the macrophage receptor for advanced glycosylation endproducts , 1987, The Journal of experimental medicine.

[28]  A. Descoteaux,et al.  The lipophosphoglycan of Leishmania parasites. , 1992, Annual review of microbiology.

[29]  A. Bacic,et al.  Identification of a macrophage-binding determinant on lipophosphoglycan from Leishmania major promastigotes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[30]  K. Chang,et al.  Molecular determinants of Leishmania virulence. , 1990, Annual review of microbiology.

[31]  A. Bacic,et al.  The glycoinositolphospholipid profiles of two Leishmania major strains that differ in lipophosphoglycan expression. , 1990, Molecular and biochemical parasitology.