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Published online 18 September 2000. doi:10.1083/jcb.150.6.1479
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© The Rockefeller University Press, 0021-9525/2000//1479 $5.00
The Journal of Cell Biology, Volume 150, Number 6, , 2000 1479-1488

Original Article

Sustained Polymorphonuclear Leukocyte Transmigration Induces Apoptosis in T84 Intestinal Epithelial Cells



Gaëlle Le'Negratea, Eric Selvaa, Patrick Aubergerb, Bernard Rossia, and Paul Hofmana,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
INSERM U364, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 01, France.33-4-93-81-94-5633-4-93-37-77-07

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.

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

© 2000 The Rockefeller University Press

Abbreviations used in this paper: CAD, caspase-activated deoxyribonuclease; DHCB, dihydrocytochalasin B; ERK, extracellular signal–regulated kinase; fMLP, N-formyl-methionyl-leucyl-phenylalanine; IBD, intestinal bowel disease; IEC, intestinal epithelial cell; PARP, poly(ADP-ribose) polymerase; PMNL, polymorphonuclear leukocyte; St, staurosporine.


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