BRONCHOALVEOLAR LAVAGE FLUID PHOSPHOLIPASE A(2) ACTIVITIES ARE INCREASED IN HUMAN ADULT-RESPIRATORY-DISTRESS-SYNDROME

The role of phospholipase A(2) (PLA(2)) in lung injury in humans is unclear. Previous studies have failed to identify an increase in PLA(2) activity in bronchoalveolar lavage fluids (BALF) of patients with the adult respiratory distress syndrome (ARDS). In this study, increased phospholipase A(2) (PLA(2)) activity was detected in BALF from patients with ARDS. PLA(2) levels in BALF correlated positively with lung injury score in patients with lung disease. BALF PLA(2) activity in patients with ARDS was resolved into heparin binding and nonbinding activities. Both PLA(2) activities were increased in BALF of ARDS patients. The PLA(2) activity that bound to heparin was identified as a group II PLA(2) by its chromatographic characteristics, its inhibition by dithiothreitol, its substrate specificity, and its approximate molecular mass of 14 kDa. The second PLA(2) activity was further purified and found to require Ca2+ at a concentration > 2 x 10(-4) M for activity. This form of PLA(2) exhibited a neutral and broad pH optimum (pH 6.0-8.0) and hydrolyzed both phospha tidylethanolamine and phosphatidylcholine effectively. Its apparent molecular mass was estimated to be 80-90 M)a. Neither anti-pancreatic PLA(2) antiserum nor anti-pig spleen cytosolic 100-kDa PLA(2) antiserum immunoprecipitated the enzymatic activity. Thus at least two forms of PLA(2) are increased in activity in BALF of patients with ARDS, a group II PLA(2) and a biochemically and immunochemically form distinct from group I, group II, and cytosolic PLA(2). Increased lung PLA(2) activity may be important for the pathophysiology of ARDS.