Neutrophil migration across intestinal epithelium: evidence for a role of CD44 in regulating detachment of migrating cells from the luminal surface.
Neutrophil migration across intestinal epithelium: evidence for a role of CD44 in regulating detachment of migrating cells from the luminal surface.
复制标题
DOI：
10.4049/jimmunol.1001293
复制
发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Louis NA
中科院分区：
文献类型：
--
作者：
Brazil JC;Lee WY;Kolegraff KN;Nusrat A;Parkos CA;Louis NA
多形核白细胞（PMN）穿过肠上皮的迁移是许多粘膜炎症性疾病（包括炎症性肠病（IBD））的组织病理学标志。最终的迁移步骤是PMN从上皮细胞的顶端表面脱离，随后释放到肠腔中。目前的研究试图确定参与调节的中性粒细胞迁移通过肠上皮细胞的阶段，中性粒细胞到达顶端上皮表面的上皮蛋白。产生一组与IFNγ刺激的T84肠上皮细胞反应的抗体。筛选工作确定了一种单克隆抗体，GM35，它可以防止PMN脱离顶端上皮表面。微测序研究将GM35抗原鉴定为人CD44。转染研究证实了这一结果，证明了GM35 mAb的功能活性的损失后，上皮CD44蛋白表达的衰减。免疫印迹和免疫荧光显示GM 35抗原是一种顶端表达的含有v6变体外显子形式的CD44（CD44v6）。ELISA分析显示，在PMN跨上皮迁移（TEM）过程中，T84细胞释放可溶性CD 44 v6。此外，所观察到的CD 44 v6释放被GM 35处理阻断，支持CD 44 v6释放和PMN脱离之间的联系。在发炎的溃疡性结肠炎组织中检测到CD44v6和GM35抗原的表达增加。本研究首次证明，上皮表达的CD44v6在炎症发作期间通过调节PMN从顶端上皮表面进入肠腔的末端脱离而在PMN清除中起作用。
The migration of polymorphonuclear leukocytes (PMN) across the intestinal epithelium is a histopathological hallmark of many mucosal inflammatory diseases including inflammatory bowel disease (IBD). The terminal transmigration step is the detachment of PMN from the apical surface of the epithelium and their subsequent release into the intestinal lumen. The current study sought to identify epithelial proteins involved in the regulation of PMN migration across intestinal epithelium at the stage where PMN reach the apical epithelial surface. A panel of antibodies reactive with IFNγ-stimulated T84 intestinal epithelial cells was generated. Screening efforts identified one mAb, GM35, which prevented PMN detachment from the apical epithelial surface. Microsequencing studies identified the GM35 antigen as human CD44. Transfection studies confirmed this result by demonstrating the loss of the functional activity of the GM35 mAb following attenuation of epithelial CD44 protein expression. Immunoblotting and immunofluoresence revealed the GM35 antigen to be an apically expressed v6 variant-exon containing form of CD44 (CD44v6). ELISA analysis demonstrated the release of soluble CD44v6 by T84 cells during PMN transepithelial migration (TEM). In addition, the observed release of CD44v6 was blocked by GM35 treatment supporting a connection between CD44v6 release and PMN detachment. Increased expression of CD44v6 and the GM35 antigen was detected in inflamed ulcerative colitis tissue. This study demonstrates for the first time that epithelial expressed CD44v6 plays a role in PMN clearance during inflammatory episodes through regulation of the terminal detachment of PMNs from the apical epithelial surface into the lumen of the intestine.
登录
查看更多内容
影响因子：
20.3
作者：
Bruyninckx, WJ;Comerford, KM;Colgan, SP
通讯作者：
Colgan, SP
DOI：
10.1084/jem.20030380
发表时间：
2003-10-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lawrence DW;Bruyninckx WJ;Louis NA;Lublin DM;Stahl GL;Parkos CA;Colgan SP
通讯作者：
Colgan SP
DOI：
10.1073/pnas.92.9.3978
发表时间：
1995-04-25
影响因子：
11.1
作者：
COOPER, D;LINDBERG, FP;VADAS, MA
通讯作者：
VADAS, MA
影响因子：
6.4
作者：
Camacho, FI;Muñoz, C;Rodríguez, R
通讯作者：
Rodríguez, R
影响因子：
4.8
作者：
COLGAN, SP;PARKOS, CA;MADARA, JL
通讯作者：
MADARA, JL