Phospholipase A2 group IIA (sPLA2-IIA) (sPLA2-IIA)

Phospholipase A2 group IIA (sPLA2-IIA), encoded by the PLA2G2A gene, is a low-molecular-weight, calcium-dependent enzyme that plays a pivotal role in lipid metabolism and the regulation of inflammatory processes [4, 15]. It catalyzes the hydrolysis of the sn-2 ester bond of phospholipids, releasing lysophospholipids and arachidonic acid, which serves as the primary precursor for the synthesis of pro-inflammatory eicosanoids such as prostaglandins and leukotrienes [1, 12]. Beyond its metabolic functions, sPLA2-IIA is a critical component of the innate immune system, exhibiting potent bactericidal activity against Gram-positive bacteria by degrading their membrane phospholipids [2, 9]. The enzyme is significantly upregulated during systemic inflammation and is considered an acute-phase reactant, with elevated levels found in patients with sepsis, rheumatoid arthritis, and cardiovascular diseases [10, 11, 13]. In addition to its catalytic role, sPLA2-IIA can function as a ligand for various cell surface receptors, including integrins and the epidermal growth factor receptor (EGFR), thereby modulating cell signaling, proliferation, and survival [15]. Therapeutic development has primarily focused on small-molecule inhibitors like varespladib to mitigate the inflammatory cascade, although clinical trials in cardiovascular disease and sepsis have faced significant hurdles, including a lack of efficacy and safety concerns [10, 14]. Recent studies have also identified sPLA2-IIA as a valuable prognostic biomarker for disease severity in infections such as COVID-19 [11, 14].

Other names

PLA2G2ASecretory phospholipase A2 group IIANon-pancreatic secretory phospholipase A2Synovial phospholipase A2Platelet-type phospholipase A2Inflammatory phospholipase A2Bactericidal phospholipase A2hGIIAPhospholipase A2, membrane associated

Inhibition of sPLA2-IIA enzymatic activity to block the release of arachidonic acid and subsequent pro-inflammatory eicosanoid production.