Intestinal epithelium is more susceptible to cytopathic injury and altered permeability than the lung epithelium in the context of acute sepsis

Mark W. Julian, Shengying Bao, Daren L. Knoell, Ruairi J. Fahy, Guohong Shao, Elliott D. Crouser

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Mitochondrial morphology and function are altered in intestinal epithelia during endotoxemia. However, it is unclear whether mitochondrial abnormalities occur in lung epithelial cells during acute sepsis or whether mitochondrial dysfunction corresponds with altered epithelial barrier function. Thus, we hypothesized that the intestinal epithelium is more susceptible to mitochondrial injury than the lung epithelium during acute sepsis and that mitochondrial dysfunction precedes impaired barrier function. Using a resuscitated feline model of Escherichia coli-induced sepsis, lung and ileal tissues were harvested after 6h for histological and mitochondrial ultrastructural analyses in septic (n=6) and time-matched controls (n=6). Human lung epithelial cells (HLEC) and Caco-2 monolayers (n=5) were exposed to 'cytomix' (TNFα: 40ng/ml, IL-1β: 20ng/ml, IFNγ: 10ng/ml) for 24-72h, and measurements of transepithelial electrical resistance (TER), epithelial permeability and mitochondrial membrane potential (ΔΨ) were taken. Lung epithelial morphology, mitochondrial ultrastructure and pulmonary gas exchange were unaltered in septic animals compared to matching controls. While histologically intact, ileal epithelia demonstrated marked mitochondrial ultrastructural damage during sepsis. Caco-2 monolayers treated with cytomix showed a significant decrease in mitochondrial ΔΨ within 24h, which was associated with a progressive reduction in TER and increased epithelial permeability over the subsequent 48h. In contrast, mitochondrial ΔΨ and epithelial barrier functions were preserved in HLEC following cytomix. These findings indicate that intestinal epithelium is more susceptible to mitochondrial damage and dysfunction than the lung epithelium in the context of sepsis. Early alterations in mitochondrial function portend subsequent epithelial barrier dysfunction.

Original languageEnglish (US)
Pages (from-to)366-376
Number of pages11
JournalInternational Journal of Experimental Pathology
Volume92
Issue number5
DOIs
StatePublished - Oct 2011

Keywords

  • Acute lung injury
  • Feline
  • Mitochondria
  • Multiple organ failure
  • Sepsis syndrome

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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