Am. J. Respir. Crit. Care Med., Volume 161, Number 5, May 2000, 1624-1630

Clara Cell Specific Protein (CC16) Expression after Acute Lung Inflammation Induced by Intratracheal Lipopolysaccharide Administration

KARIM ARSALANE, FABRICE BROECKAERT, BERNARD KNOOPS, MURIELLE WIEDIG, GERARD TOUBEAU, and ALFRED BERNARD

Unit of Industrial Toxicology and Occupational Medicine, Faculty of Medicine, Catholic University of Louvain; and Department of Histology, University of Mons-Hainaut, Brussels, Belgium

Clara cell secretory protein (CC16, CC10, or CCSP), the major secretory protein of the Clara cell, presents several biologic properties, suggesting that it may play a protective role against intrapulmonary inflammatory processes. The aim of the present study was to investigate the changes of CC16 concentrations in the lung, bronchoalveolar lavage fluid (BALF), and serum of rats with acute lung injury induced by lipopolysaccharide (LPS). These changes 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 200 µg/100 g body weight, LPS induced an acute lung inflammation as estimated by an increased influx of cells and albumin in the BALF. This inflammatory 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 bronchiolar epithelium was also decreased. In serum, by contrast, the concentration of CC16 was elevated as a consequence of increased airway permeability. Pretreating rats intraperitoneally with dexamethasone (2 mg/kg) significantly lowered 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 alveolocapillary 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.

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