Enterocyte apoptosis after enterectomy in mice is activated independent of the extrinsic death receptor pathway.
Intestinal adaptation following small bowel resection (SBR) is associated with greater rates of enterocyte apoptosis by unknown mechanism(s). Because postresection adaptation is associated with increased translocation of luminal bacteria, we sought to characterize the role for the extrinsic, death receptor pathway for the activation of enterocyte apoptosis after massive SBR. We first performed SBR or sham operations in mice, and the temporal expression of caspases 8, 9, and 3, death receptors tumor necrosis factor receptor-1 (TNFR1) and Fas and corresponding ligands (TNF and Fas ligand) was determined in the remnant intestine at various postoperative time points. Ileal TNFR1 and Fas expression were then measured after SBR in the setting of increased (waved-2 mice) or decreased (exogenous EGF administration) apoptosis. Finally, intestinal adaptation and apoptosis were recorded in the remnant ileum after SBR in TNFR1-null and Fas-null mice. The expression of death receptor family proteins and caspases demonstrated only modest changes after SBR and did not correlate with the histological appearance of apoptosis. In the setting of accelerated apoptosis, TNFR1 and Fas expression were paradoxically decreased. Apoptotic and adaptive responses were preserved in both TNFR1-null and Fas-null mice. These results suggest that the mechanism for increased enterocyte apoptosis following massive SBR does not appear to involve the extrinsic, death receptor-mediated pathway.
Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, OH 45229-3039, USA.
Andrew W
AW
Knott
David P
DP
O'Brien
Russell J
RJ
Juno
Yufang
Y
Zhang
Jodi L
JL
Williams
Christopher R
CR
Erwin
Brad W
BW
Warner
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology; D017209:Apoptosis; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000032:analysis; D020895:Enterocytes / Q000166:cytology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D053222:Fas Ligand Protein; D007421:Intestine, Small / Q000737:chemistry / Q000601:surgery*; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000172:deficiency / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019014:fas Receptor / Q000032:analysis / Q000235:genetics / Q000502:physiology
D015703:Antigens, CD; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D004815:Epidermal Growth Factor; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases