Harmful and protective roles of group V phospholipase A2: Current perspectives and future directions

Samuchiwal, Sachin K.; Balestrieri, Barbara

doi:10.1016/j.bbalip.2018.10.001

Cited by 20 publications

(20 citation statements)

References 82 publications

(138 reference statements)

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“…However, an imbalance between pro and anti-inflammatory lipids could account for the different role of Pla2g5 in the pathogenesis of several pathologies. Additionally, the expression of Pla2g5 in hematopoietic vs. non-hematopoietic cells could also determine the function of Pla2g5 in different diseases [ 25 , 26 ]. A recent study showed that in endothelial cells, the expression of Pla2g5 mRNA is higher than other PLA 2 s (Pla2g1b, 2a, 2d, 2e, 2f, and 10) then its expression is reduced by Angiotensin II stimulation while Pla2g5 protein is still present on the cell surface, likely linked to proteoglycans [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is worth noting that the constitutive and ubiquitous group IVA cytosolic PLA 2 (cPLA 2 α or Pla2g4a), which preferentially releases Arachidonic Acid (AA), is expressed more abundantly in M1 macrophages than in M2 macrophages [ 24 ]. Of the secretory PLA 2 family members, group V PLA 2 (Pla2g5) is expressed in macrophages [ 25 ] and other cells [ 26 ]. Several studies, including ours, have reported the presence of Pla2g5 mRNA and protein in bone marrow-derived macrophages (BM-Macs), peritoneal macrophages, human monocyte-derived macrophages, macrophage-cell lines [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Lipid Profile of Activated Macrophages and Contribution of Group V Phospholipase A2

et al. 2020

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Macrophages activated by Interleukin (IL)-4 (M2) or LPS+ Interferon (IFN)γ (M1) perform specific functions respectively in type 2 inflammation and killing of pathogens. Group V phospholipase A2 (Pla2g5) is required for the development and functions of IL-4-activated macrophages and phagocytosis of pathogens. Pla2g5-generated bioactive lipids, including lysophospholipids (LysoPLs), fatty acids (FAs), and eicosanoids, have a role in many diseases. However, little is known about their production by differentially activated macrophages. We performed an unbiased mass-spectrometry analysis of phospholipids (PLs), LysoPLs, FAs, and eicosanoids produced by Wild Type (WT) and Pla2g5-null IL-4-activated bone marrow-derived macrophages (IL-4)BM-Macs (M2) and (LPS+IFNγ)BM-Macs (M1). Phosphatidylcholine (PC) was preferentially metabolized in (LPS+IFNγ)BM-Macs and Phosphatidylethanolamine (PE) in (IL-4)BM-Macs, with Pla2g5 contributing mostly to metabolization of selected PE molecules. While Pla2g5 produced palmitic acid (PA) in (LPS+IFNγ)BM-Macs, the absence of Pla2g5 increased myristic acid (MA) in (IL-4)BM-Macs. Among eicosanoids, Prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2) were significantly reduced in (IL-4)BM-Macs and (LPS+IFNγ)BM-Macs lacking Pla2g5. Instead, the IL-4-induced increase in 20-carboxy arachidonic acid (20CooH AA) was dependent on Pla2g5, as was the production of 12-hydroxy-heptadecatrienoic acid (12-HHTrE) in (LPS+IFNγ)BM-Macs. Thus, Pla2g5 contributes to PE metabolization, PGE2 and PGD2 production independently of the type of activation, while in (IL-4)BM-Macs, Pla2g5 regulates selective lipid pathways and likely novel functions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipid Profile of Activated Macrophages and Contribution of Group V Phospholipase A2

et al. 2020

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“…Exogenous administration of these unsaturated fatty acids to Pla2g5 −/− mice restores IL-33-induced inflammation and ILC2 expansion, implying that macrophage-associated sPLA 2 -V contributes to type 2 immunity by promoting ILC2 activation though the release of OA and LA. The biological roles of sPLA 2 -V in asthma were summarized in a recent review [ 59 ]. Probably because of the alteration in the macrophage phenotype, Pla2g5 −/− macrophages have a reduced ability to phagocytose extracellular materials, thereby being more susceptible to fungal infection and arthritis due to defective clearance of hazardous fungi and immune complexes, respectively [ 60 , 61 ].…”

Section: The Spla 2 Familymentioning

confidence: 99%

Updating Phospholipase A2 Biology

2020

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The phospholipase A2 (PLA2) superfamily contains more than 50 enzymes in mammals that are subdivided into several distinct families on a structural and biochemical basis. In principle, PLA2 has the capacity to hydrolyze the sn-2 position of glycerophospholipids to release fatty acids and lysophospholipids, yet several enzymes in this superfamily catalyze other reactions rather than or in addition to the PLA2 reaction. PLA2 enzymes play crucial roles in not only the production of lipid mediators, but also membrane remodeling, bioenergetics, and body surface barrier, thereby participating in a number of biological events. Accordingly, disturbance of PLA2-regulated lipid metabolism is often associated with various diseases. This review updates the current state of understanding of the classification, enzymatic properties, and biological functions of various enzymes belonging to the PLA2 superfamily, focusing particularly on the novel roles of PLA2s in vivo.

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“…Role of sPLA 2 -V in ALI sPLA 2 group V (defined as sPLA 2 -V, gVPLA 2 , or PLA2G5) is less well-studied compared to sPLA 2 -IIA; however, research in the last decade has provided strong evidence that it is involved in several inflammatory disease processes [34]. In contrast to sPLA 2 -II, sPLA 2 -V has a high capacity to bind PC, a major phospholipid in the outer leaflet of the mammalian plasma membrane and pulmonary surfactant.…”

Section: Role Of Spla 2 Group Iia and Iid In Alimentioning

confidence: 99%

“…In contrast to sPLA 2 -II, sPLA 2 -V has a high capacity to bind PC, a major phospholipid in the outer leaflet of the mammalian plasma membrane and pulmonary surfactant. Some reports suggest that sPLA 2 -V preferentially releases fatty acids with a low degree of unsaturation, such as oleic and linoleic acids [11]; however, a large body of evidence also implicates sPLA 2 -V in AA mobilization and eicosanoid generation [11,[34][35][36].…”

Section: Role Of Spla 2 Group Iia and Iid In Alimentioning

confidence: 99%

Secretory Phospholipase A2 Enzymes in Acute Lung Injury

Letsiou

Htwe

Dudek

2021

Cell Biochem Biophys

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The secretory phospholipase A 2 (sPLA 2 ) group of secreted enzymes hydrolyze phospholipids and lead to the production of multiple biologically active lipid mediators. sPLA 2 s and their products (e.g., eicosanoids) play a significant role in the pathophysiology of various inflammatory diseases, including life-threatening lung disorders such as acute lung injury (ALI) and the Acute Respiratory Distress Syndrome (ARDS). The ALI/ARDS spectrum of severe inflammatory conditions is caused by direct (such as bacterial or viral pneumonia) or indirect insults (sepsis) that are associated with high morbidity and mortality. Several sPLA 2 isoforms are upregulated in patients with ARDS as well as in multiple ALI preclinical models, and individual sPLA 2 s exert unique roles in regulating ALI pathophysiology. This brief review will summarize the contributions of specific sPLA 2 isoforms as markers and mediators in ALI, supporting a potential therapeutic role for targeting them in ARDS.

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Harmful and protective roles of group V phospholipase A2: Current perspectives and future directions

Cited by 20 publications

References 82 publications

Lipid Profile of Activated Macrophages and Contribution of Group V Phospholipase A2

Lipid Profile of Activated Macrophages and Contribution of Group V Phospholipase A2

Updating Phospholipase A2 Biology

Secretory Phospholipase A2 Enzymes in Acute Lung Injury

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