Modulation of immunity by the secreted phospholipase <scp>A<sub>2</sub></scp> family

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  • Makoto Murakami
    Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan
  • Hiroyasu Sato
    Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan
  • Yoshitaka Taketomi
    Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan

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<jats:title>Summary</jats:title><jats:p>Among the phospholipase A<jats:sub>2</jats:sub> (PLA<jats:sub>2</jats:sub>) superfamily, which typically catalyzes the <jats:italic>sn</jats:italic>‐2 hydrolysis of phospholipids to yield fatty acids and lysophospholipids, the secreted PLA<jats:sub>2</jats:sub> (sPLA<jats:sub>2</jats:sub>) family contains 11 isoforms in mammals. Individual sPLA<jats:sub>2</jats:sub>s 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 sPLA<jats:sub>2</jats:sub>s 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 sPLA<jats:sub>2</jats:sub>s in given tissue microenvironments. sPLA<jats:sub>2</jats:sub>s 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 sPLA<jats:sub>2</jats:sub>s 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 sPLA<jats:sub>2</jats:sub>s in various immune responses and associated diseases.</jats:p>

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