BioProject

Ozone is a common pollutant and a potent oxidant in industrialized nations. The mechanisms of ozone-induced lung injury and differential susceptibility are not fully understood. More...

Ozone is a common pollutant and a potent oxidant in industrialized nations. The mechanisms of ozone-induced lung injury and differential susceptibility are not fully understood. Ozone-induced lung inflammation is mediated, in part, by the innate immune system. We hypothesized that mannose binding lectin (MBL), which has a central role in the activation of the complement pathway of innate immunity, is a necessary component of the pro-inflammatory events caused by ozone-mediated activation of the innate immune system. Wild-type (Mbl+/+) and MBL deficient (Mbl-/-) mice were exposed to ozone (0.3 ppm) for 24, 48, and 72 hours, and bronchoalveolar lavage fluid (BALF) was examined for inflammatory markers. Compared to Mbl+/+ mice, significantly greater mean BALF eosinophils, neutrophils and neutrophil attractants CXCL2 (MIP-2) and CXCL5 (LIX) were found in Mbl-/- mice exposed to ozone. Using genome-wide mRNA microarray analyses, we identified significant differences in expression response profiles and networks at baseline (e.g. NRF2 mediated oxidative stress response) and after exposure (e.g. humoral immune response) between Mbl+/+ and Mbl-/- mice. The microarray data were further analyzed using a pattern recognition analysis for Extracting Patterns and Identifying co-expressed Genes (EPIG), and discovered several informative differential response patterns and subsequent gene sets, including antimicrobial response and inflammatory response. These novel findings demonstrate that targeted deletion of Mbl caused differential expression of inflammation-related gene sets basally and after exposure to ozone, and significantly reduced pulmonary inflammation thus indicating an important innate immunomodulatory role of the gene in this model. Overall design: Gene expression was measured in lungs of wild type or MBL knockout mice exposed to filtered air or ozone (0.3ppm) for 24, 48, or 72 hours. Less...