Updating Phospholipase A2 Biology

Murakami, Makoto; Sato, Hiroyasu; Taketomi, Yoshitaka

doi:10.3390/biom10101457

Cited by 139 publications

(147 citation statements)

References 221 publications

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“…Macrophage functions are regulated by several PLA 2 s, including Pla2g5, Pla2g4a, Pla2g10, and Pla2g2d which may contribute to PL remodeling during activation [ 26 , 43 , 45 ]. Notably, Pla2g5 mRNA is induced in macrophages by IL-4 but not LPS+IFNγ [ 20 , 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…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: Discussionmentioning

confidence: 99%

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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“…for their catalytic activity, principally targeting phospholipids in the extracellular milieu. sPLA2s are widely distributed in different body fluids (e.g., snake and other venoms, plasma, pancreatic juice, tears, seminal fluid) and are involved in a variety of processes, from snakebite envenomation to signal transduction, to lipid mediator production and dietary lipids digestion in mammals [6,8,9]. Moreover, it is important to consider that snake venom PLA2s toxins are potential therapeutic drugs against many pathophysiological conditions [10].…”

Section: Introductionmentioning

confidence: 99%

Short Linear Motifs Characterizing Snake Venom and Mammalian Phospholipases A2

Peggion

Tonello

2021

Toxins

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Snake venom phospholipases A2 (PLA2s) have sequences and structures very similar to those of mammalian group I and II secretory PLA2s, but they possess many toxic properties, ranging from the inhibition of coagulation to the blockage of nerve transmission, and the induction of muscle necrosis. The biological properties of these proteins are not only due to their enzymatic activity, but also to protein–protein interactions which are still unidentified. Here, we compare sequence alignments of snake venom and mammalian PLA2s, grouped according to their structure and biological activity, looking for differences that can justify their different behavior. This bioinformatics analysis has evidenced three distinct regions, two central and one C-terminal, having amino acid compositions that distinguish the different categories of PLA2s. In these regions, we identified short linear motifs (SLiMs), peptide modules involved in protein–protein interactions, conserved in mammalian and not in snake venom PLA2s, or vice versa. The different content in the SLiMs of snake venom with respect to mammalian PLA2s may result in the formation of protein membrane complexes having a toxic activity, or in the formation of complexes whose activity cannot be blocked due to the lack of switches in the toxic PLA2s, as the motif recognized by the prolyl isomerase Pin1.

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“…Based on their dependence on Ca 2+ and cellular localization, these enzymes are generally classified into several families [ 4 , 5 , 6 ]. Three of these families are the most studied in terms of cellular signaling and lipid mediator production: the Ca 2+ -dependent cytosolic phospholipase A 2 s, the Ca 2+ -dependent secreted phospholipase A 2 s, and the Ca 2+ -independent phospholipase A 2 s. In this respect, the contribution by Murakami et al [ 7 ] provides a timely overview of the functioning of members of these three major phospholipase A 2 families in several pathophysiological conditions, ranging from host defense and metabolism to cancer and skin barrier function.…”

mentioning

confidence: 99%