Thomas D D, Navab M, Haake D A, Fogelman A M, Miller J N, Lovett M A
Department of Microbiology and Immunology, University of California, Los Angeles 90024.
Proc Natl Acad Sci U S A. 1988 May;85(10):3608-12. doi: 10.1073/pnas.85.10.3608.
The pathogenesis of syphilis reflects invasive properties of Treponema pallidum, but the actual mode of tissue invasion is unknown. We have found two in vitro parallels of treponemal invasiveness. We tested whether motile T. pallidum could invade host cells by determining the fate of radiolabeled motile organisms added to a HeLa cell monolayer; 26% of treponemes associated with the monolayer in a trypsin-resistant niche, presumably between the monolayer and the surface to which it adhered, but did not attain intracellularity. Attachment of T. pallidum to cultured human and rabbit aortic and human umbilical vein endothelial cells was 2-fold greater than to HeLa cells. We added T. pallidum to aortic endothelial cells grown on membrane filters under conditions in which tight intercellular junctions had formed. T. pallidum was able to pass through the endothelial cell monolayers without altering tight junctions, as measured by electrical resistance. In contrast, heat-killed T. pallidum and the nonpathogen Treponema phagedenis biotype Reiter failed to penetrate the monolayer. Transmission electron micrographs of sections of the monolayer showed T. pallidum in intercellular junctions. Our in vitro observations suggest that these highly motile spirochetes may leave the circulation by invading the junctions between endothelial cells.
梅毒的发病机制反映了梅毒螺旋体的侵袭特性，但组织侵袭的实际方式尚不清楚。我们发现了梅毒螺旋体侵袭性在体外的两种类似情况。我们通过确定添加到HeLa细胞单层的放射性标记活动生物体的命运，来测试活动的梅毒螺旋体是否能侵入宿主细胞；26%的螺旋体在一个对胰蛋白酶有抗性的生态位中与单层细胞相关联，大概是在单层细胞与其粘附的表面之间，但并未进入细胞内。梅毒螺旋体对培养的人和兔主动脉以及人脐静脉内皮细胞的附着能力比对HeLa细胞的附着能力大两倍。我们在已经形成紧密细胞间连接的条件下，将梅毒螺旋体添加到生长在膜滤器上的主动脉内皮细胞中。通过电阻测量发现，梅毒螺旋体能够穿过内皮细胞单层而不改变紧密连接。相比之下，热灭活的梅毒螺旋体和非致病性的细弱密螺旋体生物变种赖特氏菌无法穿透单层细胞。单层细胞切片的透射电子显微镜图像显示梅毒螺旋体存在于细胞间连接中。我们的体外观察结果表明，这些高度活动的螺旋体可能通过侵入内皮细胞之间的连接而离开循环系统。
