CLARA CELL PROTEIN (CC16) IN PLEURAL FLUIDS - A MARKER OF LEAKAGE THROUGH THE VISCERAL PLEURA

Pleural fluid (PF) proteins either derive from serum by diffusion or a re locally secreted within the pleural space. Another hypothetical ori gin is a leakage of lung secretory proteins across the visceral pleura . To test this hypothesis, we investigated the occurrence, sources, an d determinants in PF of CC16, a small-size and readily diffusible prot ein of 16 kDa secreted by bronchiolar Clara cells. CC16 concentration was determined by a sensitive latex immunoassay in serum and PF of 117 subjects (86 exudates and 31 transudates) and, for purpose of compari son, in ascites samples from another group of 38 subjects (7 exudates and 31 transudates). CC16 was also studied in serum and PF of normal r ats and in rats with pleural exudate induced by cr-naphthyl-thiourea ( ANTU). The levels of CC16 in PF and ascites were highly correlated wit h that in serum, suggesting a diffusional exchange across the pleural/ blood and peritoneal/blood barriers. Whereas CC16 occurs at similar le vels in ascites and serum, the protein was found to be more concentrat ed in PF than in serum in both humans (geometric mean in mu g/L, 26.2 versus 14.6, p < 0.0001) and rats (213 versus 16.2, p < 0.001). A loca l synthesis of CC16 appeared unlikely in view of the lack of CC16-immu nostaining in pleura of both species. The only plausible explanation f or these findings is that CC16 in PF originates from two sources: diff usion from plasma and a leakage from the lung into the pleural space a cross the semipermeable visceral pleura. This interpretation is suppor ted by a markedly increased leakage of CC16 in experimental exudates i nduced by ANTU and the finding of high CC16 concentrations in human tr ansudates associated with congestive heart failure, two conditions whe rein PF has been shown to arise from the interstitial spaces of the lu ng.