ARDS is a multifactorial life-threatening lung injury, characterized by diffuse lung inflammation and increased alveolocapillary barrier permeability. The different stages of ARDS have distinctive biochemical and clinical profiles. Despite the progress of our understanding on ARDS pathobiology, the mechanisms underlying its pathogenesis are still obscure. Herein, we review the existing literature about the implications of phospholipases 2 (PLA2s), a large family of enzymes that catalyze the hydrolysis of fatty acids at the sn-2 position of glycerophospholipids, in ARDS-related pathology. We emphasize on the versatile way of participation of different PLA2s isoforms in the distinct ARDS subgroup phenotypes by either potentiating lung inflammation and damage or by preserving the normal lung. Current research supports that PLA2s are associated with the progression and the outcome of ARDS. We herein discuss the transcellular communication of PLA2s through secreted extracellular vesicles and suggest it as a new mechanism of PLA2s involvement in ARDS. Thus, the elucidation of the spatiotemporal features of PLA2s expression may give new insights and provide valuable information about the risk of an individual to develop ARDS or advance to more severe stages, and potentially identify PLA2 isoforms as biomarkers and target for pharmacological intervention.
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