Roles of secreted phospholipase A2 group IIA in inflammation and host defense

Abstract Among all members of the secreted phospholipase A 2 (sPLA 2 ) family, group IIA sPLA 2 (sPLA 2 -IIA) is possibly the most studied enzyme. Since its discovery, many names have been associated with sPLA 2 -IIA, such as “non-pancreatic”, “synovial”, “platelet-type”, “inflammatory”, and “bactericidal” sPLA 2. Whereas the different designations indicate comprehensive functions or sources proposed for this enzyme, the identification of the precise roles of sPLA 2 -IIA has remained a challenge. This can be attributed to: the expression of the enzyme by various cells of different lineages, its limited activity towards the membranes of immune cells despite its expression following common inflammatory stimuli, its ability to interact with certain proteins independently of its catalytic activity, and its absence from multiple commonly used mouse models. Nevertheless, elevated levels of the enzyme during inflammatory processes and associated consistent release of arachidonic acid from the membrane of extracellular vesicles suggest that sPLA 2 -IIA may contribute to inflammation by using endogenous substrates in the extracellular milieu. Moreover, the remarkable potency of sPLA 2 -IIA towards bacterial membranes and its induced expression during the course of infections point to a role for this enzyme in the defense of the host against invading pathogens. In this review, we present current knowledge related to mammalian sPLA 2 -IIA and its roles in sterile inflammation and host defense.