Le'Negrate G, Rostagno P, Auberger P, Rossi B, Hofman P
Institut National de la Santé et de la Recherche Médicale (INSERM) U364, France.
Cell Death Differ. 2003 Feb;10(2):153-62. doi: 10.1038/sj.cdd.4401110.
During inflammatory bowel diseases, commitment of extravased polymorphonuclear leucocytes (PMN) to apoptosis is required for the resolution of inflammation. To investigate the effect of transepithelial migration on PMN apoptotic rates, PMN transepithelial migration was reproduced in vitro using T84 intestinal monolayers. Transepithelial migration was found to delay neutrophil apoptosis, and this survival effect correlated with a downregulation of the surface expression of Fas ligand (FasL) and with a decrease in both procaspases-3, and -8 mRNA and procaspases-3, -6, -7 and -8 protein levels. Moreover, neutrophil survival and FasL shedding mediated by transepithelial migration were abrogated by a broad-spectrum metalloproteinase inhibitor, BB-94. Although Erk1/2 and p38 MAPK were activated in transmigrated PMN, inhibition of these MAP kinases did not impair transmigration-induced PMN survival. Taken together, our results show that trans-epithelial migration induces the downregulation of proapoptotic proteins expression in transmigrated PMN, which results in their increased lifespan.
在炎症性肠病期间，渗出的多形核白细胞（PMN）发生凋亡是炎症消退所必需的。为了研究跨上皮迁移对PMN凋亡率的影响，利用T84肠单层细胞在体外重现了PMN跨上皮迁移过程。结果发现，跨上皮迁移会延迟中性粒细胞凋亡，这种存活效应与Fas配体（FasL）表面表达的下调以及procaspases -3和-8 mRNA水平及procaspases -3、-6、-7和-8蛋白水平的降低相关。此外，广谱金属蛋白酶抑制剂BB -94可消除跨上皮迁移介导的中性粒细胞存活和FasL脱落。虽然在迁移的PMN中Erk1/2和p38丝裂原活化蛋白激酶（MAPK）被激活，但抑制这些MAP激酶并不影响迁移诱导的PMN存活。综上所述，我们的结果表明，跨上皮迁移可诱导迁移的PMN中促凋亡蛋白表达下调，从而延长其寿命。
