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Publication : Clara cell secretory protein deficiency increases oxidant stress response in conducting airways.

First Author  Mango GW Year  1998
Journal  Am J Physiol Volume  275
Issue  2 Pt 1 Pages  L348-56
PubMed ID  9700096 Mgi Jnum  J:51081
Mgi Id  MGI:1314570 Doi  10.1152/ajplung.1998.275.2.L348
Citation  Mango GW, et al. (1998) Clara cell secretory protein deficiency increases oxidant stress response in conducting airways. Am J Physiol 275(2 Pt 1):L348-56
abstractText  Little is known about the molecular basis for differential pulmonary oxidant sensitivity observed between genetically disparate members of the same species. We have generated mice that are deficient in Clara cell secretory protein (CCSP -/-) and that exhibit an oxidant-sensitive phenotype. We characterized the kinetics and distribution of altered stress-response [interleukin-6 (IL-6) and metallothionein (MT)] and epithelial cell-specific [cytochrome P-450 2F2 (CYP2F2)] gene expression to further understand the cellular and molecular basis for altered oxidant sensitivity in 129 strain CCSP -/- mice. Increases in IL-6 and MT mRNA abundance were detected by 2 h of exposure to 1 part/million ozone and preceded reductions in Clara cell CYP2F2 mRNA expression. Despite being qualitatively similar, increases in IL-6 and MT mRNA expression were enhanced in CCSP -/- mice with respect to coexposed 129 strain wild-type mice. Increased MT mRNA expression, indicative of the stress response, localized to the airway epithelium, surrounding mesenchyme, and endothelium of blood vessels. These results demonstrate a protective role for Clara cells and their secretions and indicate potential genetic mechanisms that may influence susceptibility to oxidant stress.
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