Sustained polymorphonuclear leukocyte transmigration induces apoptosis in T84 intestinal epithelial cells.
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.
Le'Negrate
G
G
Institut National de la Santé et de la Recherche Médicale (INSERM) U364, Instituts Fédératifs de Recherche 50, Nice, France.
Selva
E
E
Auberger
P
P
Rossi
B
B
Hofman
P
P
D000199:Actins / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D053143:Caspase 2; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D003092:Colitis / Q000276:immunology / Q000503:physiopathology; D003110:Colonic Neoplasms; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004792:Enzyme Precursors / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D009504:Neutrophils / Q000166:cytology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011108:Polymers / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D000199:Actins; D004792:Enzyme Precursors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011108:Polymers; D011506:Proteins; D019014:fas Receptor; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053143:Caspase 2; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases