Neural targeting of Mycobacterium leprae mediated by the G domain of the laminin-alpha 2 chain

被引:135
作者
Rambukkana, A
Salzer, JL
Yurchenco, PD
Tuomanen, EI
机构
[1] NYU,MED CTR,DEPT CELL BIOL,NEW YORK,NY 10016
[2] NYU,MED CTR,DEPT NEUROL,NEW YORK,NY 10016
[3] NYU,MED CTR,KAPLAN CANC CTR,NEW YORK,NY 10016
[4] UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PATHOL,PISCATAWAY,NJ 08854
关键词
D O I
10.1016/S0092-8674(00)81927-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-alpha 2 (LN-alpha 2) chain on Schwann cell-axon units. Using recombinant fragments of LN-alpha 2 (rLN-alpha 2), the M. leprae-binding site was localized to the G domain. rLN-alpha PG mediated M. leprae binding to cell lines and to sciatic nerves of dystrophic dy/dy mice lacking LN-alpha 2, but expressing laminin receptors. Anti-beta(4) integrin antibody attenuated rLN-alpha 2G-mediated M. leprae adherence, suggesting that M. leprae interacts with cells by binding to beta(4) integrin via an LN-alpha 2G 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.
引用
收藏
页码:811 / 821
页数:11
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