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 indi cators of airway epithelial injury; 2) test the hypothesis that hypero xia-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 alt eration in lung permeability was estimated by changes in lung wet weig ht: dry weight ratio and total bronchoalveolar lavage (BAL) protein co ncentration. The airway inflammatory response to O2 was assessed by ch anges in cellular profiles in BAL fluid. At least two distinct phenoty pes were found among the strains exposed to O2 for 72 h. The susceptib le 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 caus ed LWW:LDW to double in susceptible B6 mice relative to controls, whil e no significant change was found in resistant C3 mice. Compared to ai r-exposed controls, hyperoxia also decreased the mean number of BAL al veolar macrophages and increased polymorphonuclear leukocytes in B6 mi ce, but the inflammatory cell profile of C3 mice was not affected afte r 72 h. The observed ratios of resistant to susceptible phenotypes of F1, F2, and back-cross progeny from B6 and C3 progenitors were not con sistent with the hypothesis that susceptibility to hyperoxia is under Mendelian control. Inter-strain differences in hyperoxic lung injury s uggest that genetic background contributes significantly to susceptibi lity, but the mode of inheritance is not clear. This model should prov e useful for investigations of mechanisms and factors that may contrib ute to the variability in pulmonary responses to O2.