Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome

Abstract

The role of phospholipase A2 (PLA2) in lung injury in humans is unclear. Previous studies have failed to identify an increase in PLA2 activity in bronchoalveolar lavage fluids (BALF) of patients with the adult respiratory distress syndrome (ARDS). In this study, increased phospholipase A2 (PLA2) activity was detected in BALF from patients with ARDS. PLA2 levels in BALF correlated positively with lung injury score in patients with lung disease. BALF PLA2 activity in patients with ARDS was resolved into heparin binding and nonbinding activities. Both PLA2 activities were increased in BALF of ARDS patients. The PLA2 activity that bound to heparin was identified as a group II PLA2 by its chromatographic characteristics, its inhibition by dithiothreitol, its substrate specificity, and its approximate molecular mass of 14 kDa. The second PLA2 activity was further purified and found to require Ca2+ at a concentration > 2 x 10(-4) M for activity. This form of PLA2 exhibited a neutral and broad pH optimum (pH 6.0-8.0) and hydrolyzed both phosphatidylethanolamine and phosphatidylcholine effectively. Its apparent molecular mass was estimated to be 80-90 kDa. Neither anti-pancreatic PLA2 antiserum nor anti-pig spleen cytosolic 100-kDa PLA2 antiserum immunoprecipitated the enzymatic activity. Thus at least two forms of PLA2 are increased in activity in BALF of patients with ARDS, a group II PLA2 and a biochemically and immunochemically form distinct from group I, group II, and cytosolic PLA2. Increased lung PLA2 activity may be important for the pathophysiology of ARDS.

Inhibitory Effects of Surfactant Protein A on Surfactant Phospholipid Hydrolysis by Secreted Phospholipases A2

“…Elevated levels of sPLA 2 activity have been reported in the BALF of patients; moreover, these levels correlated with the severity of the disease (13). However, the type of sPLA 2 s involved in ARDS has not been clearly established.…”

“…To date, 10 different sPLA 2 s, referred to as groups IB, IIA, IIC, IID, IIE, IIF, III, V, X, and XII, have been characterized in mammals (7)(8)(9)(10)(11)(12). Of particular interest, levels of sPLA 2 activity in bronchoalveolar lavage fluids (BALF) of patients with ARDS often correlate positively with the severity of the disease (13). However, the type of sPLA 2 involved in this disorder remains unclear.…”

Surfactant for Pediatric Acute Lung Injury

“…However, synthetic ether-linked lipids are now available that have direct structural analogy to lung surfactant lipids plus designed molecular behavior that enhances adsorption and spreading while maintaining very high dynamic surface tension lowering in surface films (e.g., [71,[205][206][207][208][209][210][211]). Moreover, such lipids have structural features making them resistant to phospholipases such as phospholipase A 2 , which has been implicated in the pathology of ALI/ARDS [65,[212][213][214][215][216][217][218]. Phospholipase-induced degradation of lung surfactant glycerophospholipids not only reduces the concentration of active components, but also generates reaction products such as lysophosphatidylcholine and fluid free fatty acids that can further decrease surface activity by interacting biophysically with remaining surfactant at the alveolar interface [55,59,70].…”

Phospholipase A2 in meconium-induced lung injury

“…[5][6][7][8][9] In agreement, high blood and pulmonary enzyme activity, correlating with the disease severity, has been found in acute respiratory distress in adults. 10 Although high PLA 2 activity in inflammatory lung injuries is commonly connected with increased release of group II secretory PLA 2 (PLA 2 -II) from macrophages and platelets, 6,7,11 group I PLA 2 (PLA 2 -I), secreted by the pancreas, is also known to be expressed and to modulate cellular function in human lungs. 12 Mammalian PLA 2 -I is in fact able to inactivate pulmonary surfactant concentration-dependently through hydrolysis of phosphatidylcholine.…”