ReviewImmunology

Enzymatically oxidized phospholipids assume center stage as essential regulators of innate immunity and cell death

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Science Signaling  26 Mar 2019:
Vol. 12, Issue 574, eaau2293
DOI: 10.1126/scisignal.aau2293

Gloss

Lipids that are generated by enzymes in circulating blood cells through controlled oxidation of biomembranes have been discovered. These lipids, called enzymatically oxidized phospholipids (eoxPLs), are made when blood cells are activated, for example, during an injury that leads to blood clotting. Although they are needed for defense against disease, it is now believed that their formation within blood vessels can contribute to several forms of inflammation, such as in atherosclerosis, diabetes, and arthritis. In this Review with 104 references and 5 figures, we summarize the new research that led to the discovery of eoxPLs and what we know so far about the roles of these lipids in health and disease.

Abstract

Enzymatically oxidized phospholipids (eoxPLs) are formed through regulated processes by which eicosanoids or prostaglandins are attached to phospholipids (PLs) in immune cells. These eoxPLs comprise structurally diverse families of biomolecules with potent bioactivities, and they have important immunoregulatory roles in both health and disease. The formation of oxPLs through enzymatic pathways and their signaling capabilities are emerging concepts. This paradigm is changing our understanding of eicosanoid, prostaglandin, and PL biology in health and disease. eoxPLs have roles in cellular events such as ferroptosis, apoptosis, and blood clotting and diseases such as arthritis, diabetes, and cardiovascular disease. They are increasingly recognized as endogenous bioactive mediators and potential targets for drug development. This review will describe recent evidence that places eoxPLs and their biosynthetic pathways center stage in immunoregulation.

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