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持续的多形核白细胞迁移诱导T84肠上皮细胞凋亡。

Sustained polymorphonuclear leukocyte transmigration induces apoptosis in T84 intestinal epithelial cells.

作者信息

Le'Negrate G, Selva E, Auberger P, Rossi B, Hofman P

机构信息

Institut National de la Santé et de la Recherche Médicale (INSERM) U364, Instituts Fédératifs de Recherche 50, Nice, France.

出版信息

J Cell Biol. 2000 Sep 18;150(6):1479-88. doi: 10.1083/jcb.150.6.1479.

DOI:10.1083/jcb.150.6.1479
PMID:10995451
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2150691/
Abstract

Acute colitis is characterized by a large number of polymorphonuclear leukocytes (PMNLs) migrating across the columnar epithelium in response to inflammatory stimuli. Several of these inflammatory factors have been characterized as proapoptotic inducers for intestinal epithelial cells. Our aim was to elucidate the role of PMNL transmigration in the onset of intestinal epithelial cell apoptosis. We found that PMNL migration, in response to N-formyl-methionyl-leucyl-phenylalanine across monolayers of intestinal epithelial cells (T84), was associated with activation of caspase-2, -3, and -9 and poly(ADP-ribose) polymerase cleavage within epithelial cells. Moreover, dihydrocytochalasin B treatment of T84 cells induced apoptosis with similar characteristics. Although Fas and Fas ligand were expressed on T84 cells and PMNLs, treatment of epithelial cells with an antagonistic anti-Fas antibody failed to prevent apoptosis induced by migrating PMNLs. Owing to the F-actin reorganization accompanying PMNL transmigration, these findings indicate a direct relationship between PMNL migration and induction of apoptosis in epithelial cells. This apoptotic process appears to involve remodeling of the actin cytoskeleton of enterocytes independent of the Fas/Fas ligand pathway.

摘要

急性结肠炎的特征是大量多形核白细胞（PMNLs）在炎症刺激下穿过柱状上皮迁移。其中一些炎症因子已被确定为肠道上皮细胞的促凋亡诱导剂。我们的目的是阐明PMNL迁移在肠道上皮细胞凋亡起始中的作用。我们发现，响应N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸，PMNL在肠道上皮细胞（T84）单层上的迁移与上皮细胞内半胱天冬酶-2、-3和-9的激活以及聚（ADP-核糖）聚合酶的切割有关。此外，用二氢细胞松弛素B处理T84细胞可诱导具有相似特征的细胞凋亡。尽管Fas和Fas配体在T84细胞和PMNLs上表达，但用拮抗抗Fas抗体处理上皮细胞并不能阻止迁移的PMNLs诱导的细胞凋亡。由于伴随PMNL迁移的F-肌动蛋白重组，这些发现表明PMNL迁移与上皮细胞凋亡诱导之间存在直接关系。这种凋亡过程似乎涉及肠上皮细胞肌动蛋白细胞骨架的重塑，且独立于Fas/Fas配体途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/fcc24577bb84/JCB0002105.f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/99445d238d85/JCB0002105.f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/b7fe2e37ea8c/JCB0002105.f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/a3696b870a17/JCB0002105.f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/a5fb3925a70a/JCB0002105.f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/d13423ed3bd7/JCB0002105.f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/249c73865ba7/JCB0002105.f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/7b313bc58286/JCB0002105.f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/fcc24577bb84/JCB0002105.f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/99445d238d85/JCB0002105.f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/b7fe2e37ea8c/JCB0002105.f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/a3696b870a17/JCB0002105.f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/a5fb3925a70a/JCB0002105.f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/d13423ed3bd7/JCB0002105.f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/249c73865ba7/JCB0002105.f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/7b313bc58286/JCB0002105.f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2534/2150691/fcc24577bb84/JCB0002105.f8.jpg

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