Increased enterocyte apoptosis and Fas-Fas ligand system in celiac disease

Rachele Ciccocioppo, Antonio Di Sabatino, Raffaella Parroni, Paola Muzi, Simona D'Alò, Terenzio Ventura, Maria Antonietta Pistoia, Maria Grazia Cifone, Gino Roberto Corazza

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Our aim was to evaluate whether increased enterocyte apoptosis was responsible for mucosal flattening in celiac disease (CD), and, since the mechanisms responsible for tissue injury in this condition are unknown, we studied the possibility that the Fas-Fas ligand (FasL) system may be involved. Endoscopic duodenal biopsy specimens from 12 patients with untreated and 12 with treated CD and 12 control subjects were evaluated for enterocyte apoptosis by the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick-end labeling assay and for Fas and FasL expression by immunohistochemistry. A coculture of isolated enterocytes (targets) and purified lamina propria mononuclear cells (LPMCs) (effectors) was performed in the absence or presence of an antagonistic ZB4 anti-Fas antibody. We found a significant correlation between the degree of villous atrophy, morphometrically evaluated, and the level of enterocyte apoptosis, suggesting that mucosal flattening is a consequence of exaggerated epithelial cell death. Most celiac enterocytes express Fas, and LPMCs express FasL. The abolishment of enterocyte apoptosis observed in the presence of ZB4 antibody suggests that enterocytes are potential targets of lymphocyte infiltrate. These results directly demonstrate that FasL-mediated apoptosis is a major mechanism responsible for enterocyte death in CD.

Original languageEnglish
Pages (from-to)494-503
Number of pages10
JournalAmerican Journal of Clinical Pathology
Volume115
Issue number4
DOIs
Publication statusPublished - Apr 2001

Fingerprint

Fas Ligand Protein
Enterocytes
Celiac Disease
Apoptosis
Mucous Membrane
Digoxigenin
DNA Nucleotidylexotransferase
Coculture Techniques
Abdomen
Atrophy
Anti-Idiotypic Antibodies
Cell Death
Epithelial Cells
Immunohistochemistry
Lymphocytes
Biopsy
Antibodies
Wounds and Injuries

Keywords

  • Apoptosis
  • Celiac disease
  • Ceramide
  • Fas-FasL system
  • Lamina propria mononuclear cells
  • Mucosal morphometry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Increased enterocyte apoptosis and Fas-Fas ligand system in celiac disease. / Ciccocioppo, Rachele; Di Sabatino, Antonio; Parroni, Raffaella; Muzi, Paola; D'Alò, Simona; Ventura, Terenzio; Pistoia, Maria Antonietta; Cifone, Maria Grazia; Corazza, Gino Roberto.

In: American Journal of Clinical Pathology, Vol. 115, No. 4, 04.2001, p. 494-503.

Research output: Contribution to journalArticle

Ciccocioppo, Rachele ; Di Sabatino, Antonio ; Parroni, Raffaella ; Muzi, Paola ; D'Alò, Simona ; Ventura, Terenzio ; Pistoia, Maria Antonietta ; Cifone, Maria Grazia ; Corazza, Gino Roberto. / Increased enterocyte apoptosis and Fas-Fas ligand system in celiac disease. In: American Journal of Clinical Pathology. 2001 ; Vol. 115, No. 4. pp. 494-503.
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