Acute injury to differentiating clara cells in neonatal rabbits results in age-related failure of bronchiolar epithelial repair

Suzette M. Smiley-Jewell, Frank J. Liu, Alison J. Weir, Charles Plopper

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Nonciliated bronchiolar (Clara) cells are progenitor cells during lung development. During differentiation, they have a heightened injury susceptibility to environmental toxicants bioactivated by cytochrome P450 monooxygenase. When neonatal rabbits are treated with the P450-mediated cytotoxicant 4-ipomeanol (IPO), abnormal bronchiolar epithelium results. This study establishes the impact of IPO cytotoxicity on 3 stages of rabbit Clara cell differentiation, early (2.5 and 5 days postnatal [DPN]), intermediate (7 and 9 DPN), and late (15 and 21 DPN), and relates the cytotoxicity to the extent of bronchiolar repair. Neonates received a single dose of IPO (5 mg/kg) and were assessed by qualitative pathology 48 hours later for injury or at 4 weeks for repair. IPO injured the 3 stages of Clara cell differentiation to the same degree; epithelium was swollen, exfoliated, and squamated. Epithelial repair differed among the 3 stages. Bronchioles of animals treated during early and intermediate stages had simple squamous and irregularly shaped cuboidal cells. Animals treated during late stages were similar to controls. Thus, differentiating Clara cells are susceptible to injury by the P450-mediated cytotoxicant IPO, but the extent of repair varies based on when the initial injury occurs.

Original languageEnglish (US)
Pages (from-to)267-276
Number of pages10
JournalToxicologic Pathology
Volume28
Issue number2
DOIs
StatePublished - Jan 1 2000

Keywords

  • 4-ipomeanol
  • Cell differentiation
  • Clara cell
  • lung development
  • neonatal
  • P450 metabolism

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

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