Susceptibility to ozone-induced inflammation. II. Separate loci control responses to acute and subacute exposures

S. R. Kleeberger, R. C. Levitt, L. Y. Zhang

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


We demonstrated previously that inbred strains of mice are differentially susceptible to acute (3 h) and subacute (48 h) exposures to 2 parts per million (ppm) ozone (O3) and 0.30 ppm O3, respectively. Genetic studies with O3-resistant C3H/HeJ and O3-susceptible C57BL/6J strains have indicated that susceptibility to each of these O3 exposures is under Mendelian (single gene) control. In the present study, we hypothesized that the same gene controls susceptibility to the airway inflammatory responses to 2 ppm and 0.30 ppm O3 exposures. To test this hypothesis, airway inflammation was induced in 10 BXH and 16 BXD recombinant inbred (RI) strains of mice by acute as well as subacute O3 exposures. Airway inflammation was assessed by counting the number of polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage (BAL) returns obtained immediately after 48-h subacute exposure to 0.30 ppm O3, or 6 h after 3 h acute exposure to 2 ppm O3. Each RI strain was classified as susceptible or resistant to each exposure, based on a comparison of mean numbers of PMNs with those of the respective progenitor strains. For each RI set, a phenotypic strain distribution pattern (SDP) was thus derived for each exposure regimen, and the SDPs were then compared for concordance. Among the BXH RI strains, 4 of 10 responded discordantly to the two exposures: 3 were susceptible to acute exposure and resistant to subacute exposure, whereas 1 was conversely susceptible. Among the BXD RI strains, 4 of 16 were discordant: 1 was susceptible to acute exposure, and resistant to subacute exposure, whereas 3 were conversely susceptible. These cosegregation analyses suggest that genes at more than one loci likely control susceptibility to the two O3 exposures: Inf, acute exposures; Inf-2, subacute exposures. Analyses also imply that mechanisms that confer differential susceptibility to acute O3 are not necessarily predictive of susceptibility to subacute O3 exposures.

Original languageEnglish (US)
Pages (from-to)L21-L26
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 8-1
StatePublished - 1993
Externally publishedYes


  • airways
  • BXD recombinant inbred mice
  • BXH recombinant inbred mice
  • C3H/HeJ mice
  • C57BL/6J mice
  • cosegregation analysis
  • DBA/2J mice
  • genetics
  • polymorphonuclear leukocytes
  • recombinant inbred strains
  • segregant progeny
  • susceptibility

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine


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