Inter-strain variation in susceptibility to hyperoxic injury of murine airways.
The contribution of genetic background in susceptibility to hyperoxic lung injury is not clear. We utilized inbred mice to: 1) characterize inter-strain variation in hyperoxia-induced effects on lavageable indicators of airway epithelial injury; 2) test the hypothesis that hyperoxia-induced change in airway permeability is under Mendelian control. Male mice (5-7 wk, 20-25 g) from six inbred strains were exposed to 95-99% oxygen (O2) or room air for 0, 48, or 72 h. Hyperoxia-induced alteration in lung permeability was estimated by changes in lung wet weight:dry weight ratio and total bronchoalveolar lavage (BAL) protein concentration. The airway inflammatory response to O2 was assessed by changes in cellular profiles in BAL fluid. At least two distinct phenotypes were found among the strains exposed to O2 for 72 h. The susceptible phenotype (exemplified by C57BL/6J [B6] mice) was characterized by mean BAL protein concentration that was approximately 10 times greater than the resistant phenotype (e.g. C3H/HeJ [C3] mice). Hyperoxia caused LWW:LDW to double in susceptible B6 mice relative to controls, while no significant change was found in resistant C3 mice. Compared to air-exposed controls, hyperoxia also decreased the mean number of BAL alveolar macrophages and increased polymorphonuclear leukocytes in B6 mice, but the inflammatory cell profile of C3 mice was not affected after 72 h. The observed ratios of resistant to susceptible phenotypes of F1, F2, and back-cross progeny from B6 and C3 progenitors were not consistent with the hypothesis that susceptibility to hyperoxia is under Mendelian control.(ABSTRACT TRUNCATED AT 250 WORDS)
Hudak
B B
BB
Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Zhang
L Y
LY
Kleeberger
S R
SR
D000818:Animals; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000378:metabolism; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D008171:Lung Diseases / Q000209:etiology / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010100:Oxygen / Q000633:toxicity*; D010641:Phenotype; D011506:Proteins / Q000378:metabolism
D011506:Proteins; D010100:Oxygen