Function of secreted phospholipase A2 group-X in asthma and allergic disease

Abstract

Elevated secreted phospholipase A 2 (sPLA 2) activity in the airways has been implicated in the pathogenesis of asthma and allergic disease for some time. The identity and function of these enzymes in asthma is becoming clear from work in our lab and others. We focused on sPLA 2 group X (sPLA 2-X) after identifying increased levels of this enzyme in asthma, and that it is responsible for a large portion of sPLA 2 activity in the airways and that the levels are strongly associated with features of airway hyperresponsiveness (AHR). In this review, we discuss studies that implicated sPLA 2-X in human asthma, and murine models that demonstrate a critical role of this enzyme as a regulator of type-2 inflammation, AHR and production of eicosanoids. We discuss the mechanism by which sPLA 2-X acts to regulate eicosanoids in leukocytes, as well as effects that are mediated through the generation of lysophospholipids and through receptormediated functions.

Lipid storm within the lungs of severe COVID-19 patients: Extensive levels of cyclooxygenase and lipoxygenase-derived inflammatory metabolites

“…in (55)), the increased levels of LA, EPA and DHA support the idea that other phospholipases A 2 are also heavily involved in the lipidome we have quantitated. Those additional phospholipases likely belong to the superfamily of secreted phospholipases A 2 , which can hydrolyze phospholipids containing fatty acids other than AA (56, 57) and are reported to contribute to lung inflammation (58-61). However, and assuming that a large part of eicosanoids is the consequence of the group IVA cytosolic phospholipase A 2, our findings do not allow us to pinpoint which other phospholipases are involved in the release of LA, AA, EPA, DPA and DHA.…”

Updating Phospholipase A2 Biology

“…Interestingly, as in the case of bee venom group III sPLA 2 that elicits strong type-2 immune responses, exogenous administration of sPLA 2 -X serves as an adjuvant, leading to augmented type-2 immune responses with increased airway hypersensitivity and antigen-specific type-2 inflammation following peripheral sensitization and subsequent airway challenge with the antigen [ 75 ]. The biological roles of sPLA 2 -X in asthma were detailed in a recent review [ 76 ].…”

Current perspective on eicosanoids in asthma and allergic diseases: EAACI Task Force consensus report, part I

“…Eicosanoids, docosanoids, and related oxygenated derivatives mainly originate from arachidonic acid (AA), dihomo‐γ‐linolenic acid (DHGLA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) 5–7 . These precursor fatty acids are cleaved from membrane phospholipids by cytosolic phospholipase A 2 α (cPLA 2 group 4A) and to a lesser extent by secreted forms of PLA 2 (sPLA 2 ) upon various stimuli 8–13 . Next, free fatty acids are metabolized by three main pathways: cyclooxygenases (COXs), lipoxygenases (LOs or LOXs), or cytochrome P450, giving rise to different families of mediators 14,15 (Figure 1A).…”

“…[5][6][7] These precursor fatty acids are cleaved from membrane phospholipids by cytosolic phospholipase A 2 α (cPLA 2 group 4A) and to a lesser extent by secreted forms of PLA 2 (sPLA 2 ) upon various stimuli. [8][9][10][11][12][13] Next, free fatty acids are metabolized by three main pathways: cyclooxygenases (COXs), lipoxygenases (LOs or LOXs), or cytochrome P450, giving rise to different families of mediators 14,15 ( Figure 1A).…”