Phospholipases A2 and platelet-activating-factor acetylhydrolase in patients with acute respiratory distress syndrome

Objective. Phospholipases A(2) (PLA(2)) comprise a family of enzymes probably implicated in the development of acute respiratory distress syndrome (ARDS). The aim was to investigate PLA2 activities and characteristics in bronchoalveolar lavage (BAL) fluid, BAL cells, and plasma from patients with ARDS by a fluorometric method. Design: Prospective, controlled study. Setting: Fourteen-bed polyvalent intensive care unit in a university hospital. Patients: A total of 31 mechanically ventilated patients, 20 with and 11 without ARDS, were studied. Intervention. BAL was performed by fiberoptic bronchoscopy in mechanically ventilated patients with a controlled mechanical ventilation mode. Measurements: PLA(2) and platelet-activating-factor acetylhydrolase were determined in BAL fluid, cells, and plasma. For the classification of PLA(2)-specific inhibitors, Western blot analysis and their biochemical characteristics were used. Results: In ARDS patients, increased PLA(2) levels were detected in BAL fluid, BAL cells, and plasma compared with the control patients. PLA(2) in BAL fluid was mainly type IIA secretory and cytosolic types. In plasma, type IIA secretory and cytosolic and a Ca2+-independent PLA(2) were found. In BAL cells, a cytosolic form, probably a Ca2+-independent intracellular form, and a low activity of type IIA secretory PLA(2) was also observed. Total PLA(2) activity correlated inversely with Pao(2)/Fio(2) ratio and positively with the mortality rate. Patients with direct ARDS exhibited higher PLA(2) activity compared with patients with indirect ARDS. Platelet-activating-factor acetylhydrolase activity was higher in BAL fluid and plasma, but it was lower in BAL cells. Conclusion. Ca2+-dependent secretory, cytosolic, and Ca2+-independent forms of PLA(2) and platelet-activating-factor acetylhydrolase could play important roles in the development or down-regulation of inflammation in ARDS, respectively.