Cao Thong V, La Mylinh, Getting Stephen J, Day Anthony J, Perretti Mauro
The William Harvey Research Institute, Bart's and the London Queen Mary School of Medicine and Dentistry, London, UK.
Microcirculation. 2004 Oct-Nov;11(7):615-24. doi: 10.1080/10739680490503438.
The authors investigated whether the anti-inflammatory protein tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) and its Link module (Link_TSG6) could affect the complex multistep process of leukocyte/endothelial cell (EC) interaction.
Mouse mesenteries were inflamed with interleukin (IL)-1beta and the extent of leukocyte rolling, adhesion, and emigration was determined after 2 h. Link_TSG6 and a single-point mutant (termed K13E) were given intraperitoneally together with the cytokine. Human neutrophil chemotaxis and transmigration were determined in vitro in response to IL-8 and/or TNF-alpha. TSG-6, Link_TSG6, and K13E were added to the leukocytes or the EC monolayers.
Co-injection of Link_TSG6 with IL-1beta selectively inhibited cell flux, adhesion, and emigration as analyzed in mesenteric postcapillary venules. The fewer cells that rolled in the animals treated with Link_TSG6 displayed a velocity similar to that measured in vehicle-treated mice. In vitro, Link_TSG6 did not affect neutrophil chemotaxis or EC activation but did inhibit neutrophil transmigration across EC monolayers. The latter effect was shared by full-length TSG-6 and observed equally in response to IL-8 or TNF-alpha.
These data restrict the site of action for at least some of the anti-inflammatory effects ascribed to TSG-6/Link_TSG6 to the microenvironment of the extravasating leukocyte.
作者研究了抗炎蛋白肿瘤坏死因子（TNF）刺激基因-6（TSG-6）及其连接模块（Link_TSG6）是否会影响白细胞/内皮细胞（EC）相互作用这一复杂的多步骤过程。
用白细胞介素（IL）-1β使小鼠肠系膜发生炎症，2小时后测定白细胞滚动、黏附和移出的程度。将Link_TSG6和单点突变体（称为K13E）与细胞因子一起腹腔注射。体外测定人中性粒细胞对IL-8和/或TNF-α的趋化性和迁移情况。将TSG-6、Link_TSG6和K13E添加到白细胞或EC单层中。
如在肠系膜后微静脉中所分析的，Link_TSG6与IL-1β共同注射可选择性抑制细胞流量、黏附和移出。在接受Link_TSG6治疗的动物中滚动的细胞较少，其速度与在接受赋形剂治疗的小鼠中测得的速度相似。在体外，Link_TSG6不影响中性粒细胞趋化性或EC活化，但可抑制中性粒细胞跨EC单层的迁移。全长TSG-6也有后一种作用，并且在对IL-8或TNF-α的反应中同样观察到。
这些数据将至少部分归因于TSG-6/Link_TSG6的抗炎作用的作用位点限制在渗出白细胞的微环境中。
