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

Abstract

Ca-dependent, secretory, cytosolic, and Ca-independent forms of PLA2 and platelet-activating-factor acetylhydrolase could play important roles in the development or down-regulation of inflammation in ARDS, respectively.

Surfactant protein B inhibits secretory phospholipase A2hydrolysis of surfactant phospholipids

“…For this reason, PLA2GIB was selected for these initial studies, which aimed to assess how general were the effects of SP-B reduction on hydrolysis by sPLA 2 . Although PLA2GIB is a human pancreatic sPLA 2 that may account for increased sPLA 2 activity in ALI/ARDS cases associated with pancreatitis, it does not likely account for the majority of increased sPLA 2 activity in either the bronchoalveolar lavage fluid or serum of the majority of ALI/ARDS cases not associated with pancreatitis (35). PLA2G1B was cloned from lung tissue (46) and was reported to increase in both stimulated Type II cells maintained in tissue culture (3) and in murine epithelial cells in response to Pseudomonas aeruginosa (1).…”

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].…”

Multiple Roles of Phospholipase A2during Lung Infection and Inflammation

“…ARDS patients experience an increase in PAF-AH during the acute phase of the disease and a reduction at later stages, suggesting that plasma PAF-AH may be important for the resolution of ARDS (40,85). In a rat model of ARDS, rPAF-AH administration serves to blunt alveolar macrophage inflammatory responses (16).…”