Genetic susceptibility to irritant-induced acute lung injury in mice

Scott C. Wesselkamper, Daniel R. Prows, Pratim Biswas, Klaus Willeke, Eula Bingham, George D. Leikauf

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Recent studies suggest that genetic variability can influence irritant-induced lung injury and inflammation. To begin identifying genes controlling susceptibility to inhaled irritants, seven inbred mouse strains were continuously exposed to nickel sulfate (NiSO4), polytetrafluoroethylene, or ozone (O3), and survival time was recorded. The A/J (A) mouse strain was sensitive, the C3H/He (C3) strain was intermediate, and the C57BL/6 (B6) strain was resistant to NiSO4-induced acute lung injury. The B6AF1 offspring were also resistant. The strain sensitivity pattern for NiSO4 exposure was similar to that of polytetrafluoroethylene or ozone (O3). Pulmonary pathology was comparable for A and B6 mice. In the A strain, 15 μg/m3 of NiSO4 produced 20% mortality. The strain sensitivity patterns for lavage fluid proteins (B6 > C3 > A) and neutrophils (A ≥ B6 > C3) differed from those for acute lung injury. This phenotype discordance suggests that these traits are not causally linked (i.e., controlled by independent arrays of genes). As in acute lung injury, B6C3F1 offspring exhibited phenotypes (lavage fluid proteins and neutrophils) resembling those of the resistant parental strain. Agreement of acute lung injury strain sensitivity patterns among irritants suggested a common mechanism, possibly oxidative stress, and offspring resistance suggested that sensitivity is inherited as a recessive trait.

Original languageEnglish (US)
Pages (from-to)L575-L582
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume279
Issue number3 23-3
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Acute respiratory distress syndrome
  • Air pollution
  • Asthma
  • Bronchitis
  • Environmental genetics
  • Nickel
  • Oxidant
  • Ozone
  • Particulate matter

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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