EFFECT OF MONOCLONAL ANTIBODIES ANTI-GLYCOSPHINGOLIPIDS IN PATHOGENIC FUNGAL DEVELOPMENT
Toledo MS; Suzuki E; Tagliari L; Straus AH; Takahashi HK
Universidade Federal de São Paulo, Dept. of Biochemistry, R. Botucatu 862, Ed. JL Prado, São Paulo, SP, Brazil
The general increase of fungal infections, particularly in immunocompromised patients, has raised the interest in identifying new targets for fungal immunodiagnosis and therapy. It has been shown in the literature that antibodies directed to ceramide monohexosyl affects fungal growth and differentiation (Rodrigues et al., Infect Immun, 2000, 68). In order to analyze the possible role of neutral and acidic GSLs as targets to antibody-based therapy, in this study it was analyzed three monoclonal antibodies (mAbs): i) mAb MEST-1 (anti-Galfb1®3/6Manp); ii) mAb MEST-2 (fungal anti-GlcCer); and iii) a recently described mAb, termed MEST-3 (IgG2a), directed to Paracoccidioides brasiliensis GIPC Pb-2 (Manpa1®3Manpa1®2Ins1-P-1Cer). The fine specificity of mAb MEST-3 was defined as: Manpa1®3Manpa1®2Ins. By indirect immunofluorescence using mAb MEST-3, it was observed strong staining of yeast forms of P. brasiliensis, Histoplasma capsulatum, and Sporothrix schenckii. On the other hand, no fluorescence was observed in mycelium forms of these fungi.
Studies using MEST-1, -2 and –3 mAbs as fungal growth inhibitors showed that anti-GIPCs mAbs (MEST-1 and -3) presented a strong inhibitory activity on growth, differentiation and colony formation of P. brasiliensis, H. capsulatum, and S. schenckii. On the other hand, it was observed weak inhibition using anti-GlcCer (MEST-2). As expected MEST-1 was not able to inhibit S. schenckii growth, since this mycopathogen does not express GIPCs bearing the epitope recognized by MEST-1. These results strongly suggest that mAbs directed to glycosphingolipids are able to interfere on fungal growth/differentiation. Surface expression of GIPC/GlcCer in yeast and mycelium forms of fungi may yield more information regarding the relevance of GSLs expression in the processes of fungal growth, morphological transition, and infectivity. Supported by FAPESP, CAPES and CNPq
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