Rambukkana A, Salzer J L, Yurchenco P D, Tuomanen E I
Laboratory of Molecular Infectious Diseases, The Rockefeller University, New York, New York 10021, USA.
Cell. 1997 Mar 21;88(6):811-21. doi: 10.1016/s0092-8674(00)81927-3.
We report that the molecular basis of the neural tropism of Mycobacterium leprae is attributable to the specific binding of M. leprae to the laminin-alpha2 (LN-alpha2) chain on Schwann cell-axon units. Using recombinant fragments of LN-alpha2 (rLN-alpha2), the M. leprae-binding site was localized to the G domain. rLN-alpha2G mediated M. leprae binding to cell lines and to sciatic nerves of dystrophic dy/dy mice lacking LN-alpha2, but expressing laminin receptors. Anti-beta4 integrin antibody attenuated rLN-alpha2G-mediated M. leprae adherence, suggesting that M. leprae interacts with cells by binding to beta4 integrin via an LN-alpha2G bridge. Our results indicate a novel role for the G domain of LN-2 in infection and reveal a model in which a host-derived bridging molecule determines nerve tropism of a pathogen.
我们报告称，麻风分枝杆菌神经嗜性的分子基础归因于麻风分枝杆菌与施万细胞 - 轴突单元上的层粘连蛋白 -α2（LN -α2）链的特异性结合。利用重组的LN -α2片段（rLN -α2），将麻风分枝杆菌结合位点定位到G结构域。rLN -α2G介导麻风分枝杆菌与细胞系以及缺乏LN -α2但表达层粘连蛋白受体的营养不良性dy/dy小鼠的坐骨神经结合。抗β4整合素抗体减弱了rLN -α2G介导的麻风分枝杆菌黏附，这表明麻风分枝杆菌通过经由LN -α2G桥与β4整合素结合而与细胞相互作用。我们的结果表明LN -2的G结构域在感染中具有新作用，并揭示了一种宿主衍生的桥接分子决定病原体神经嗜性的模型。
