Sustained Polymorphonuclear Leukocyte Transmigration Induces Apoptosis in T84 Intestinal Epithelial Cells

doi:10.1083/jcb.150.6.1479

Published online 18 September 2000. doi:10.1083/jcb.150.6.1479

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© The Rockefeller University Press, 0021-9525/2000/9/1479/ $5.00
The Journal of Cell Biology, Volume 150, Number 6, September 18, 2000 1479-1488

Original Article

Sustained Polymorphonuclear Leukocyte Transmigration Induces Apoptosis in T84 Intestinal Epithelial Cells

Gaëlle Le'Negrate^a, Eric Selva^a, Patrick Auberger^b, Bernard Rossi^a, and Paul Hofman^a,c
^a Institut National de la Santé et de la Recherche Médicale (INSERM) U364, Instituts Fédératifs de Recherche 50
^b INSERM U526, Instituts Fédératifs de Recherche 50
^c Department of Pathology, University of Nice, 06107 Nice Cedex 01, France

Correspondence to: Paul Hofman, INSERM U364, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 01, France. Tel:33-4-93-37-77-07 Fax:33-4-93-81-94-56

Acute colitis is characterized by a large number of polymorphonuclearleukocytes (PMNLs) migrating across the columnar epitheliumin response to inflammatory stimuli. Several of these inflammatoryfactors have been characterized as proapoptotic inducers forintestinal epithelial cells. Our aim was to elucidate the roleof PMNL transmigration in the onset of intestinal epithelialcell apoptosis. We found that PMNL migration, in response toN-formyl-methionyl-leucyl-phenylalanine across monolayers ofintestinal epithelial cells (T84), was associated with activationof caspase-2, -3, and -9 and poly(ADP-ribose) polymerase cleavagewithin epithelial cells. Moreover, dihydrocytochalasin B treatmentof T84 cells induced apoptosis with similar characteristics.Although Fas and Fas ligand were expressed on T84 cells andPMNLs, treatment of epithelial cells with an antagonistic anti-Fasantibody 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 migrationand induction of apoptosis in epithelial cells. This apoptoticprocess appears to involve remodeling of the actin cytoskeletonof enterocytes independent of the Fas/Fas ligand pathway.

Key Words: colitis, apoptosis, caspases, Fas, cytoskeleton

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