Vitamin A deficiency enhances ozone-induced lung injury.

The present study determined the effects of vitamin A (vA) deficiency on the responses to ozone (O3) challenges in two inbred strains of mice that are differentially susceptible to O3-induced lung inflammation. Susceptible C57BL/6J (B6) and resistant C3H/HeJ (C3) dams at 2 wk gestation were fed test diets containing either 0 or 10 micrograms retinol/g diet. In mice that were maintained on vA-sufficient (vA+) diet, lung and liver tissue concentrations of vA and retinyl palmitate (RP) were significantly (P<0.05) lower in the B6 strain compared with C3, as measured by high-performance liquid chromatography techniques. vA and RP levels were significantly (P<0.05) reduced in lung and liver tissues of 8-wk old B6 and C3 mice that were maintained on a vA deficient (vA-) diet. vA+ and vA- mice of both strains were exposed to air or 0.3 ppm O3/72 h, and lung injury was assessed by differential cell count and total protein concentration in bronchoalveolar lavage (BAL) returns. O3 exposure caused significantly (P<0.05) greater increases in inflammatory cells and a total protein in BAL returns of vA+ B6 mice than vA+ C3 mice. vA deficiency significantly (P<0.05) enhanced O3-induced increases in polymorphonuclear leukocytes in C3 mice and epithelial cells loss in both strains. Compared with vA+ mice, lung permeability was also significantly (P<0.05) enhanced in vA- mice of both strains exposed to O3. vA replacement partially reversed the O3-induced lung injury that was enhanced by vA- diet. Results indicate that vA may have an important role in the pathogenesis of O3-induced lung injury in differentially susceptible inbred strains of mice.