Abstract

Secreted phospholipase A₂ (sPLA₂) molecules constitute a family of proteins that are involved functionally in many biological processes. In particular, they participate in diverse pathophysiological settings as enzymes that release free fatty acids and lysophospholipids from phospholipids in biological membranes, or as ligands for various cellular receptors. In this review the confirmed or expected functions of sPLA₂s in the mammalian immune system are surveyed. Some of the twelve mammalian sPLA₂ molecules constitute part of the so-called innate immune system by virtue of their antibacterial, antiviral and antifungal activities. They are also involved in acute inflammation, a protective reaction of the body to infection or injury. The acute inflammation sometimes escapes regulation, becomes chronic and can evolve into a severe pathology. One or more types of sPLA₂ are involved in asthma, rheumatoid arthritis, sepsis, atherosclerosis, myocardial infarction, Crohn’s disease, ulcerative colitis and cancer. sPLA₂s are thus important therapeutic targets as well as biotherapeutic molecules. Improving the selectivity of inhibitors of sPLA₂s to be able to target a particular sPLA₂ could therefore be one of the most important tasks for future research.

Keywords: Acute inflammation, bacterial defence, chronic inflammation, fungal defence, inflammation-related diseases, innate immunity, secreted phospholipase A₂, sPLA₂ inhibitors, viral defence.

Graphical Abstract