Susceptibility to ozone-induced inflammation. I. Genetic control of the response to subacute exposure.
We demonstrated previously that C57BL/6J (B6) inbred mice are susceptible and C3H/HeJ (C3) mice are resistant to airway inflammation that is induced by acute (3 h) exposure to 2 parts per million (ppm) ozone (O3). In the present study we tested the hypothesis that B6 and C3 mice are also differentially susceptible to the airway inflammatory responses to subacute (72 h) exposure to environmentally relevant concentrations of O3 (0.12 and 0.30 ppm). Male mice (20-25 g, 5-7 wk) were exposed continuously to 0.12 ppm O3, 0.30 ppm O3, or filtered air (control). Pulmonary inflammation was assessed after 24, 48, and 72 h by differential cell count and total protein in bronchoalveolar lavage (BAL) returns. Exposure to 0.12 ppm O3 caused significant influx of alveolar macrophages, polymorphonuclear leukocytes (PMNs), lymphocytes, and total BAL protein in both strains, but no differences in the magnitude of the responses were found between B6 and C3 mice. In contrast to the effect of 0.12 ppm O3, exposure to 0.30 ppm O3 elicited significantly greater numbers of inflammatory cells and BAL protein concentration in B6 mice relative to C3 mice. The phenotypes of the B6 and C3 mice were termed susceptible and resistant, respectively. To further evaluate the potential genetic contribution to the inflammatory response to 0.30 ppm O3, the F1, F2, and backcross progeny from B6 and C3 progenitors were examined. The ratios of susceptible and resistant phenotypes of these progeny support the hypothesis that a single autosomal recessive gene confers susceptibility to subacute O3-induced inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)
Kleeberger
S R
SR
Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Levitt
R C
RC
Zhang
L Y
LY
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006824:Hybridization, Genetic; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000008:administration & dosage / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D013997:Time Factors
D011506:Proteins; D010126:Ozone