Clara cell protein as a marker of Clara cell damage and bronchoalveolar blood barrier permeability

The 16 kDa Clara cell protein (CC16), an abundant component of airway secre tions, has recently been proposed in humans as a pulmonary marker measurabl e not only in bronchoalveolar lavage fluid (BALF) but also in serum. The ai m of the present study was to investigate the changes and determinants of C C16 concentrations in these fluids in normal rats and rats with lung injury , Female Sprague-Dawley rats were given a single ip. injection of arachis oil (n=20) or chemicals in arachis oil (n=10) that mainly damage Clara cells ( 4-ipomeanol (IPO) 8 mg.kg(-1) and methylcyclopentadienyl manganese tricarbo nyl (MMT) 5 mg.kg(-1)) or endothelial cells (alpha-naphthylthiourea (ANTU) 5 mg.kg(-1)). CC16 concentration (mean+/-SD in mu g.L-1), measured by a sensitive latex i mmunoassay, was significantly reduced in BALF of all treated groups (IPO 38 0+/-100; MMT 730+/-200; ANTU 1,070+/-200; controls 1,700+/-470). The same p attern of decrease was observed in the labelling of Clara cells with an ant i-CC16 antiserum as well as in the CC16 messenger ribonucleic acid levels a ssessed by Northern enzyme-linked immunosorbent assay. In serum, by contras t, CC16 was significantly increased in all treated groups (IPO 31+/-7; MMT 22+/-12; ANTU 52+/-24; controls 15+/-6). This rise of CC16 in serum was ass ociated,vith an elevation of albumin in BALF which is an index of increased bronchoalveolar/blood barrier permeability. In conclusion, lung injury induces a decrease of the 16 kDa Clara cell prot ein in bronchoalveolar lavage fluid owing to a reduced production by damage d Clara cells, and an increase in serum protein levels resulting from its e nhanced leakage across the bronchoalveolar/blood barrier. This study provid es new insights into the understanding of the changes of lung secretory pro teins in bronchoalveolar lavage fluid and serum.