Altered lung gene expression in CCSP-null mice suggests immunoregulatory roles for Clara cells

Clara cell secretory protein (CCSP) is one of the most abundant proteins pr esent in airway lining fluid of mammals. In an effort to elucidate the func tion of CCSP, we established CCSP-null [CCSP(-/-)] mice and demonstrated al tered sensitivity to various environmental agents including oxidant polluta nts and microorganisms. Although CCSP deficiency itself may be central to t he observed changes in environmental susceptibility, altered lung gene expr ession associated with CCSP deficiency may contribute to the observed pheno type. To determine whether CCSP deficiency results in altered lung gene exp ression, high-density cDNA microarrays were used to profile gene expression in the total lung RNA of wild-type and CCSP(-/-) mice. Genes that were dif ferentially expressed between wild-type and CCSP(-/-) mice included a previ ously nonannotated expressed sequence tag (EST W82219) and immunoglobulin A (IgA), both of which were elevated with CCSP deficiency. mRNA expression o f EST W82219 and IgA was localized in the lungs of wild-type and CCSP(-/-) mice to airway Clara cells and peribronchial lymphoid tissues, respectively . We conclude that CCSP deficiency is associated with 1) altered gene expre ssion in Clara cells of the conducting airway epithelium and 2) alterations to peribronchial B lymphocytes. These findings identify new roles for Clar a cells and their secretions in airway homeostasis.