Gesztesi J L, Puccia R, Travassos L R, Vicentini A P, de Moraes J Z, Franco M F, Lopes J D
Disciplina de Imunologia, Universidade Federal de São Paulo, Brazil.
Hybridoma. 1996 Dec;15(6):415-22. doi: 10.1089/hyb.1996.15.415.
The surface glycoprotein gp43, a highly immunogenic component of Paracoccidioides brasiliensis, is used in the serodiagnosis of paracoccidioidomycosis (PCM) and has recently been shown to specifically bind the extracellular matrix protein laminin. Binding to laminin induces the increased adhesion of the fungus to epithelial cells; a hamster testicle infection model has shown that the gp43-dependent binding of fungal cells to laminin enhances their pathogenicity in vivo. We report on the 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. Results suggest that P. brasiliensis propagules may start infection in man by strongly adhering to human lung cells. Thus, laminin-mediated fungal adhesion to human lung carcinoma (A549) cells was much more intense than to Madin-Darby canine kidney cells (MDCK), indicating differences in binding affinity. Subsequent growth of fungi bound to the lung cells could induce the granulomatous inflammatory reaction characteristic of PCM. Both steps are greatly stimulated by laminin binding in infective cells expressing gp43.
表面糖蛋白gp43是巴西副球孢子菌的一种高度免疫原性成分，用于副球孢子菌病（PCM）的血清学诊断，最近已证明它能特异性结合细胞外基质蛋白层粘连蛋白。与层粘连蛋白的结合会诱导真菌与上皮细胞的粘附增加；仓鼠睾丸感染模型表明，真菌细胞与层粘连蛋白的gp43依赖性结合会增强其在体内的致病性。我们报告了12种针对gp43的单克隆抗体的产生和特性，这些抗体识别该分子中的肽序列，检测至少三种不同的表位以及该抗原的不同亚型。单克隆抗体通过抑制或增强肉芽肿形成和组织破坏来干扰体内真菌的致病性。结果表明，巴西副球孢子菌繁殖体可能通过强烈粘附于人类肺细胞而在人体内引发感染。因此，层粘连蛋白介导的真菌与人肺癌（A549）细胞的粘附比与犬肾细胞（MDCK）的粘附强烈得多，表明结合亲和力存在差异。与肺细胞结合的真菌的后续生长可诱导PCM特有的肉芽肿性炎症反应。在表达gp43的感染细胞中，层粘连蛋白结合极大地刺激了这两个步骤。
