Clava cell specific protein (CC16) expression after acute lung inflammation induced by intratracheal lipopolysaccharide administration

Clara cell secretory protein (CC16, CC10, or CCSP), the major secretory pro tein of the Clara cell, presents several biologic properties, suggesting th at it may play a protective role against intrapulmonary inflammatory proces ses. The aim of the present study was to investigate the changes of CC16 co ncentrations in the lung, bronchoalveolar lavage fluid (BALF), and serum of rats with acute lung injury induced by lipopolysaccharide (LPS). These cha nges were compared with Clara cell density, CC16 mRNA level in the lung and classic indices of inflammation in BALF. Injected at doses of 10,100, or 2 00 mu g/100 g body weight, LPS induced an acute lung inflammation as estima ted by an increased influx of cells and albumin in the BALF. This inflammat ory response was associated with a marked reduction of CC16 concentrations in BALF and lung homogenate as well as of the CC16 mRNA levels in the lung. At the highest dose of LPS, the CC16-positive cell density in the bronchio lar epithelium was also decreased. In serum, by contrast, the concentration of CC16 was elevated as a consequence of increased airway permeability. Pr etreating rats intraperitoneally with dexamethasone (2 mg/kg) significantly towered the leukocyte influx and attenuated the albumin increase in BALF. Dexamethasone, however, failed to prevent the increased airway permeability to CC16, suggesting that during inflammation different mechanisms regulate the leakage of proteins across the alveolo-capillary barrier depending on the direction of passage and/or the size of the protein. Our results show a marked decrease of the secretion and synthesis of CC16 during LPS-induced acute lung inflammation.