Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen

Nolin, James D.; Lü, Ying; Ogden, Herbert Luke; Manicone, Anne M.; Murphy, Ryan; An, Dowon; Frevert, Charles W.; Ghomashchi, Farideh; Naika, Gajendra S.; Gelb, Michael H.; Gauvreau, Gail M.; Piliponsky, Adrian M.; Altemeier, William A.; Hallstrand, Teal S.

doi:10.1172/jci.insight.94929

Cited by 33 publications

(44 citation statements)

References 81 publications

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“…Pla2g10 −/− mice are protected from antigen-induced asthma, with marked reductions of airway hyperresponsiveness, eosinophil and T cell trafficking to the airways, airway occlusion, secretion of type-2 cytokines, generation of antigen-specific IgE, and synthesis of pulmonary eicosanoids including cysteinyl leukotrienes [ 73 ]. Further, Pla2g10 −/− mice have reduced IL-33 levels and fewer ILC2 cells in the lung, lower IL-33-induced IL-13 expression in mast cells, and a marked reduction in both the number of newly recruited macrophages and the M2 polarization of these macrophages in the lung [ 74 ]. These results indicate that sPLA 2 -X serves as a key regulator of both innate and adaptive immune responses to allergens.…”

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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Section: The Spla 2 Familymentioning

confidence: 99%

Updating Phospholipase A2 Biology

2020

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“…Quantitative data obtained using these analytical techniques can then be correlated with other measurements such as clinical data or data collected with flow cytometry or quantitative PCR. 25,29,54,55 More importantly, these morphometric techniques provide spatial information that is lost when tissues are disrupted to obtain cells for flow cytometry and proteins or mRNA for proteomics and transcriptomics studies, respectively.…”

Section: Stereology Vs Image Analysismentioning

confidence: 99%

The Use of Quantitative Digital Pathology to Measure Proteoglycan and Glycosaminoglycan Expression and Accumulation in Healthy and Diseased Tissues

Davis

Chang

Brune

et al. 2020

J Histochem Cytochem.

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Advances in reagents, methodologies, analytic platforms, and tools have resulted in a dramatic transformation of the research pathology laboratory. These advances have increased our ability to efficiently generate substantial volumes of data on the expression and accumulation of mRNA, proteins, carbohydrates, signaling pathways, cells, and structures in healthy and diseased tissues that are objective, quantitative, reproducible, and suitable for statistical analysis. The goal of this review is to identify and present how to acquire the critical information required to measure changes in tissues. Included is a brief overview of two morphometric techniques, image analysis and stereology, and the use of artificial intelligence to classify cells and identify hidden patterns and relationships in digital images. In addition, we explore the importance of preanalytical factors in generating high-quality data. This review focuses on techniques we have used to measure proteoglycans, glycosaminoglycans, and immune cells in tissues using immunohistochemistry and in situ hybridization to demonstrate the various morphometric techniques. When performed correctly, quantitative digital pathology is a powerful tool that provides unbiased quantitative data that are difficult to obtain with other methods.

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“…7 Phospholipase A2 inhibitor (PLI) synthesized by the snake liver is a kind of glycoprotein that can specifically bind to the central region of PLA2. 8 At present, 21 kinds of PLI are identified in snake serum based on the ExPASY protein database. 9 PLI can also be divided into three categories: PLIα, PLI-β, and PLI-γ.…”

Section: Introductionmentioning

confidence: 99%

<p>Effects of Snake-Derived Phospholipase A2 Inhibitors on Acute Pancreatitis: In vitro and in vivo Characterization</p>

Liao

et al. 2020

DDDT

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Objective: We aimed to investigate the effects of snake-derived phospholipase A2 inhibitor (PLA2) from Sinonatrix percarinata and Bungarus multicinctus on acute pancreatitis in vivo and in vitro and assess the mechanisms. Methods: The levels of platelet-activating factor (PAF) and tumor necrosis factor (TNF)-α were detected by ELISA, and the characteristics of autophagy were detected by transmission electron microscopy and Western blotting (LC3, p62, and ATG5). Results: In vitro experiments showed that PLA2 treatment caused obvious formation of autophagic bodies. By contrast, Sinonatrix and Bungarus peptides reduced the number of autophagic bodies. The concentrations of PAF and TNF-α, and the expressions of p62, autophagy-related 5 (ATG5), and microtubule-associated protein 1A/1B-light chain 3 (LC3)II/LC3I in the PLA2-treated group were significantly higher than in the control group (P<0.05). The concentrations of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I in the Sinonatrix or Bungarus peptide treatment groups were significantly lower than in the PLA2treated cells (P<0.05). In the pancreatic tissue, autophagic bodies were observed in the model group; autophagic bodies were remarkably reduced in Sinonatrix or Bungarus peptide-treated groups compared with the model group. In vivo experiments also showed that the levels of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I were significantly higher in the model group than in the control group (P<0.05). The levels of PAF and TNF-α in the model group, and the expressions of p62, ATG5, and LC3II/LC3I in Sinonatrix or Bungarus peptidetreated groups were significantly lower than in the model group (P<0.05). Conclusion: Sinonatrix or Bungarus peptide could ameliorate the features of acute pancreatitis, likely through regulating autophagy.

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Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen

Cited by 33 publications

References 81 publications

Updating Phospholipase A2 Biology

Updating Phospholipase A2 Biology

The Use of Quantitative Digital Pathology to Measure Proteoglycan and Glycosaminoglycan Expression and Accumulation in Healthy and Diseased Tissues

<p>Effects of Snake-Derived Phospholipase A2 Inhibitors on Acute Pancreatitis: In vitro and in vivo Characterization</p>

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