Modulation of immunity by the secreted phospholipase A₂ family

Abstract

SummaryAmong the phospholipase A2 (PLA2) superfamily, which typically catalyzes the sn‐2 hydrolysis of phospholipids to yield fatty acids and lysophospholipids, the secreted PLA2 (sPLA2) family contains 11 isoforms in mammals. Individual sPLA2s have unique enzymatic specificity toward fatty acids and polar heads of phospholipid substrates and display distinct tissue/cellular distributions, suggesting their distinct physiological functions. Recent studies using knockout and/or transgenic mice for a full set of sPLA2s have revealed their roles in modulation of immunity and related disorders. Application of mass spectrometric lipidomics to these mice has enabled to identify target substrates and products of individual sPLA2s in given tissue microenvironments. sPLA2s hydrolyze not only phospholipids in the plasma membrane of activated, damaged or dying mammalian cells, but also extracellular phospholipids such as those in extracellular vesicles, microbe membranes, lipoproteins, surfactants, and dietary phospholipids, thereby exacerbating or ameliorating various diseases. The actions of sPLA2s are dependent on, or independent of, the generation of fatty acid‐ or lysophospholipid‐derived lipid mediators according to the pathophysiological contexts. In this review, we make an overview of our current understanding of the roles of individual sPLA2s in various immune responses and associated diseases.

Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on health

“…PLA2G1B is a secreted phospholipase A2 produced by pancreatic acinar cells, that hydrolyses phosphoglycerides to glycerophospholipids and arachidonic acid 49 . Pla2g1b knock-out mice display reduced phospholipid digestion and concurrent attenuation of diet-induced obesity, insulin resistance, and atherosclerosis, while pancreatic acinar cell-specific overexpression of Pla2g1b has been linked to increased phospholipid digestion and to exacerbation of diet-induced obesity and insulin resistance 49 . PLA2G1B is currently being investigated in clinical trials for a range of cardiometabolic conditions ( Table S1 ).…”

Balancing Act of the Intestinal Antimicrobial Proteins on Gut Microbiota and Health

“…In the GI tract, it is synthesized in Paneth cells and is thought to play a role in regulating the gut microbiome (Senegas-Balas et al, 1984 ). The subsequent review delves into a more comprehensive examination of the function of sPLA2-IIA (Murakami et al, 2023 ).…”

1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit

“…Phospholipase A2 (PLA2) and IL-6 are predictive markers for the severity of COVID-19 [172]. PLA2 cleaves the sn-2 acyl chain to yield fatty acids and lysophospholipids, leading to the production of a wide variety of mediators that modulate immunity [181] and stimulate SARS-CoV-2 infection [182]. For example, PLA2 contributes to anti-helminth defense by hydrolyzing membrane phospholipids (Th2-defence, production of IL4 and IL5 cytokines, allergy/asthma) [181].…”