POTENTIAL ROLE OF CLARA CELL PROTEIN, AN ENDOGENOUS PHOSPHOLIPASE A(2) INHIBITOR, IN ACUTE LUNG INJURY

It is now recognized that epithelial cells Lining airways and alveoli are capable of releasing various mediators, which have the potential t o modulate local inflammatory reactions, The amount of the 16 kDa Clar a cell protein (CC16), an inhibitor of phospholipase A(2) activity pro duced by pulmonary epithelial cells, was measured by means of a sensit ive immunoassay in the unconcentrated bronchoalveolar lavage fluid (BA LF) of 13 control subjects, and in patients with acute lung injury (14 with the full-blown adult respiratory distress syndrome (ARDS); 21 af ter standard cardiopulmonary bypass surgery, a known risk factor for A RDS), The level of CC16 was compared with other markers of inflammatio n with a wide range of molecular weights: albumin (nephelometry); tota l protein (spectrophotometry); beta(2)-microglobulin (latex immunoassa y); cystatin C (latex immunoassay); alpha(1)-antitrypsin (immuno-radio metry), and Lipocortin-l (enzyme-linked immunosorbent assay (ELISA)). The Clara cell protein (CC16) was detectable in all BALF, and signific antly higher levels of this protein were observed in BALF from patient s with acute lung injury, Changes in BALF Clara cell protein levels di ffered from those of alpha(2)-macroglobulin and the natural phospholip ase inhibitor lipocortin-l, Alpha,macroglobulin levels were not signif icantly enhanced in patients at risk for ARDS, but were increased in p atients with ARDS; whereas, Lipocortin 1 levels were not elevated in e ither group, Pretreatment of patients at risk for ARDS with high dose methylprednisolone did not alter the amount of Clara cell protein reco vered in BALL, The mean CC16 level in BALF from patients with ARDS who died was significantly lower than from those who survived, The data p resented in this study suggest that pulmonary epithelial cells secrete a natural anti-inflammatory protein during acute lung injury, which m ight have a protective and immunosuppressive role.