Phospholipase A2, membrane associated (sPLA2-IIA) (sPLA2-IIA)

Phospholipase A2, membrane associated (sPLA2-IIA) is a low-molecular-weight, calcium-dependent enzyme that belongs to the secretory phospholipase A2 family [1, 11]. It primarily functions by hydrolyzing the sn-2 ester bond of phospholipids in cell membranes and lipoproteins, leading to the release of free fatty acids, such as arachidonic acid, and lysophospholipids [1, 13]. These products serve as precursors for potent inflammatory mediators, including prostaglandins and leukotrienes, positioning sPLA2-IIA as a key amplifier of the inflammatory response [4, 10]. Beyond its role in lipid metabolism, sPLA2-IIA exhibits significant antimicrobial activity, particularly against Gram-positive bacteria, due to its highly cationic nature which allows it to penetrate bacterial cell walls [4, 6]. In clinical contexts, elevated levels of sPLA2-IIA are associated with various inflammatory diseases, including sepsis, rheumatoid arthritis, and cardiovascular disease, as well as several types of cancer [7, 12, 16]. Therapeutic strategies have focused on small-molecule inhibitors like varespladib to mitigate chronic inflammation; however, clinical trials in cardiovascular disease were halted due to safety concerns and lack of efficacy [10, 17]. Consequently, sPLA2-IIA remains a significant biomarker for systemic inflammation and a complex target for drug development [12, 18].

Other names

Human group IIA secretory phospholipase A2PLA2G2AGroup IIA secretory phospholipase A2Non-pancreatic secretory phospholipase A2Synovial fluid phospholipase A2Platelet-type phospholipase A2Phosphatidylcholine 2-acylhydrolase 2AGIIC sPLA2

Competitive inhibition of the enzyme's catalytic active site, preventing the hydrolysis of phospholipids and the subsequent release of pro-inflammatory lipid mediators [10, 14].