Phospholipase A2 subclasses in acute respiratory distress syndrome

Abstract

Phospholipases A2 (PLA2) catalyse the cleavage of fatty acids esterified at the sn-2 position of glycerophospholipids. In acute lung injury-acute respiratory distress syndrome (ALI-ARDS) several distinct isoenzymes appear in lung cells and fluid. Some are capable to trigger molecular events leading to enhanced inflammation and lung damage and others have a role in lung surfactant recycling preserving lung function: Secreted forms (groups sPLA2-IIA, -V, -X) can directly hydrolyze surfactant phospholipids. Cytosolic PLA2 (cPLA2-IVA) requiring Ca2+ has a preference for arachidonate, the precursor of eicosanoids which participate in the inflammatory response in the lung. Ca(2+)-independent intracellular PLA2s (iPLA2) take part in surfactant phospholipids turnover within alveolar cells. Acidic Ca(2+)-independent PLA2 (aiPLA2), of lysosomal origin, has additionally antioxidant properties, (peroxiredoxin VI activity), and participates in the formation of dipalmitoyl-phosphatidylcholine in lung surfactant. PAF-AH degrades PAF, a potent mediator of inflammation, and oxidatively fragmented phospholipids but also leads to toxic metabolites. Therefore, the regulation of PLA2 isoforms could be a valuable approach for ARDS treatment.

Long-chain Acyl-CoA Dehydrogenase Deficiency as a Cause of Pulmonary Surfactant Dysfunction

“…Our lung explant studies showed normal rates of choline incorporation into total lipid, but we did not investigate trafficking of lamellar bodies and extracellular release of surfactant material. With regard to degradation, we found no observable increase in PLA 2 , which actively degrades phospholipids and is known to be increased in lavage fluid of children with RDS (66). Albumin, however, was consistently increased in LCAD Ϫ/Ϫ lavage fluid, and albumin has been shown to inactivate surfactant and to possess a phospholipase-like activity (67,68).…”

Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process

“…Activation of cytosolic phospholipase A 2 in IR mobilizes arachidonic acid for degradation by two main enzymes, lipoxygenase and cyclooxygenase, into several mediators (see below), and these initiate the production of PAF (48). Alveolar macrophages (2) are believed to play a major role in surfactant degradation through excreting lysosomal phospholipase A 2 (108) and are suggested to be responsible for decreased lung compliance after alveolar macrophage depletion with clodronate in a mouse model (212). Type II secreted phospholipase A 2 is another phospholipase A 2 , present in alveolar macrophages, but also in platelets and other cells (108).…”

“…Alveolar macrophages (2) are believed to play a major role in surfactant degradation through excreting lysosomal phospholipase A 2 (108) and are suggested to be responsible for decreased lung compliance after alveolar macrophage depletion with clodronate in a mouse model (212). Type II secreted phospholipase A 2 is another phospholipase A 2 , present in alveolar macrophages, but also in platelets and other cells (108). A relation has been found between the activation of this type II secreted phospholipase A 2 and subsequent degradation of surfactant (14).…”

Anti-inflammatory and antioxidant properties of Eriobotrya japonica leaves extracts

“…The sPLA2 group IIA was initially detected in synovial fluid of patients with rheumatoid arthritis 15,16 . Several studies demonstrated that the sPLA2 group IIA was involved in inflammatory process [17][18][19] and many phospholipases A2 inhibitors have been discovered and their effectiveness have been proved as a treatment of inflammatory diseases [20][21][22] . Because overproduction of these inflammatory mediators might cause inflammatory damage, we focused in the present study on the evaluation of the anti-inflammatory effect of LEJ extracts by measuring the inhibition of the pro-inflammatory sPLA2 group IIA as well as their antioxidant activity.…”