A genetic model for evaluation of susceptibility to ozone-induced inflammation

S. R. Kleeberger, D. J.P. Bassett, G. J. Jakab, R. C. Levitt

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

We examined ozone-induced airway inflammatory responses in inbred mice, and progeny of crosses between them, to investigate genetic susceptibility to ozone. Nine strains of male mice (18-23 g, 5-7 wk) were exposed for 3 h to 2 ppm ozone (O3) or filtered air (control) and pulmonary inflammation was assessed 2, 6, and 24 h after exposure by inflammatory cell counts and total protein content in bronchoalveolar lavage (BAL). The time course of the response to O3 was consistent between the strains. The maximum change in polymorphonuclear leukocytes (PMNs) was detected 6 h after O3, and the maximum increase in BAL protein occurred 24 h postexposure. Air controls exhibited no detectable changes in the parameters of inflammation at any time. The phenotypes of the C57BL/6J (B6, termed susceptible) and C3H/HeJ (C3, termed resistant) strains were easily distinguished by the magnitude of their inflammatory responses to O3. A 22-fold difference in PMNs was detected between the two strains 2 h after O3 (P < 0.001), and a sixfold difference was found 6 h after O3 (P < 0.001). Total BAL proteins were also significantly different between the B6 and C3 strains 6 h (P < 0.01) and 24 h after O3 (P < 0.001). To further evaluate the potential genetic contribution to the inflammatory response, the F1, F2, and backcross progeny from crosses between B6 and C3 strains were examined. The phenotypes of these progeny were consistent with the hypothesis that a single autosomal recessive gene at the Inf locus confers susceptibility to acute O3-induced influx of PMNs, but the genetic control of altered permeability is not clear. This model will be very useful for understanding mechanisms of O3-induced inflammation and factors that may influence susceptibility to oxidants.

Original languageEnglish (US)
Pages (from-to)L313-L320
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume258
Issue number6 2-3
DOIs
StatePublished - 1990

Keywords

  • airways
  • bronchoalveolar lavage
  • genetics
  • inbred mice
  • permeability
  • polymorphonuclear leukocytes

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine

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