MONOCLONAL-ANTIBODIES AGAINST THE 43,000 DA GLYCOPROTEIN FROM PARACOCCIDIOIDES-BRASILIENSIS MODULATE LAMININ-MEDIATED FUNGAL ADHESION TO EPITHELIAL-CELLS AND PATHOGENESIS

The surface glycoprotein gp43, a highly immunogenic component of Parac occidioides brasiliensis, is used in the serodiagnosis of paracoccidio idomycosis (PCM) and has recently been shown to specifically bind the extracellular matrix protein laminin, Binding to laminin induces the i ncreased adhesion of the fungus to epithelial cells; a hamster testicl e infection model has shown that the gp43-dependent binding of fungal cells to laminin enhances their pathogenicity in vivo. We report on th e production and characterization of 12 monoclonal antibodies against the gp43 that recognize peptide sequences in the molecule detecting at least three different epitopes as well as different isoforms of this antigen. MAbs interfered in the fungal pathogenicity in vivo either by inhibiting or enhancing granuloma formation and tissue destruction, R esults suggest that P. brasiliensis propagules may start infection in man by strongly adhering to human lung cells, Thus, laminin-mediated f ungal adhesion to human lung carcinoma (A549) cells was much more inte nse than to Madin-Darby canine kidney cells (MDCK), indicating differe nces in binding affinity, Subsequent growth of fungi bound to the lung cells could induce the granulomatous inflammatory reaction characteri stic of PCM. Both steps are greatly stimulated by laminin binding in i nfective cells expressing gp43.