Regulation and function of CCSP during pulmonary Pseudomonas aeruginosa infection in vivo

Clara cell secretory protein (CCSP) is a 16-kDa homodimeric polypeptide sec reted by respiratory epithelial cells in the conducting airways of the lung . To assess the role of CCSP in bacterial inflammation and to discern wheth er CCSP expression is influenced by bacterial infection, CCSP-deficient [(- /-)] gene-targeted mice and wild-type mice were given Pseudomonas aeruginos a intratracheally. Infiltration by polymorphonuclear cells was significantl y increased in the lungs of CCSP(-/-) mice 6 and 24 h after the administrat ion of the bacteria. The number of viable bacteria isolated from the lungs in CCSP(-/-) mice was decreased compared with that in wild-type mice. Conce ntrations of the proinflammatory cytokines interleukin-1 alpha and tumor ne crosis factor-alpha were modestly increased after 6 and 24 h, respectively, in CCSP(-/-) mice. The concentration of CCSP protein in lung homogenates d ecreased for 1-5 days after infection and recovered by 14 days after infect ion. Likewise, CCSP mRNA and immunostaining for CCSP markedly decreased in respiratory epithelial cells after infection. CCSP deficiency was associate d with enhanced pulmonary inflammation and improved killing of bacteria aft er acute pulmonary infection with P. aeruginosa. The finding that Pseudomon as infection inhibited CCSP expression provides further support for the con cept that CCSP plays a role in the modulation of pulmonary inflammation dur ing infection and recovery.