Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients with Mastocytosis

Background. Mastocytosis is a condition characterized by the expansion and accumulation of mast cells (MCs) in various organs. The symptoms are related to the increased release of MC-derived mediators that exert local and distant effects. MCs are a source and target of phospholipase enzymes (PLs), w...

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Main Authors: Anne Lise Ferrara, Fabiana Piscitelli, Angelica Petraroli, Roberta Parente, Maria Rosaria Galdiero, Gilda Varricchi, Giancarlo Marone, Massimo Triggiani, Vincenzo Di Marzo, Stefania Loffredo
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/5836476
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author Anne Lise Ferrara
Fabiana Piscitelli
Angelica Petraroli
Roberta Parente
Maria Rosaria Galdiero
Gilda Varricchi
Giancarlo Marone
Massimo Triggiani
Vincenzo Di Marzo
Stefania Loffredo
author_facet Anne Lise Ferrara
Fabiana Piscitelli
Angelica Petraroli
Roberta Parente
Maria Rosaria Galdiero
Gilda Varricchi
Giancarlo Marone
Massimo Triggiani
Vincenzo Di Marzo
Stefania Loffredo
author_sort Anne Lise Ferrara
collection DOAJ
description Background. Mastocytosis is a condition characterized by the expansion and accumulation of mast cells (MCs) in various organs. The symptoms are related to the increased release of MC-derived mediators that exert local and distant effects. MCs are a source and target of phospholipase enzymes (PLs), which catalyze the cleavage of membrane phospholipids releasing lipid mediators (e.g., diacylglycerols (DAGs) and the endocannabinoid (EC) 2-arachidonoylglycerol (2-AG)). To date, there are no data on the role of these lipid mediators in mastocytosis. Here, we analyzed plasma levels of PLA2, PLC, DAG, ECs, and EC-related N-acylethanolamines in patients with mastocytosis. Methods. In 23 patients with mastocytosis and 23 healthy individuals, we measured plasma PLA2 and PLC activities, DAG, 2-AG, anandamide (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA). Results. Plasma PLA2 and PLC activities were increased in mastocytosis patients compared to controls. Concentrations of DAG (18:1 20:4 and 18:0 20:4), two second messengers produced by PLC, were higher in mastocytosis compared to controls, whereas the concentrations of their metabolite, 2-AG, were not altered. AEA was decreased in mastocytosis patients compared to controls; by contrast, AEA congener, PEA, was increased. PLA2 and PLC activities were increased only in patients with mediator-related symptoms. Moreover, PLC activity was positively correlated with disease severity and tryptase concentrations. By contrast, AEA was negatively correlated with tryptase concentrations. Conclusions. PLs and some lipid mediators are altered in patients with mastocytosis. Our results may pave the way for investigating the functions of these mediators in the pathophysiology of mastocytosis and provide new potential biomarkers and therapeutic targets.
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spelling doaj-art-8e34b858cd43422c8106a8181c2beb012025-08-20T03:37:17ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/58364765836476Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients with MastocytosisAnne Lise Ferrara0Fabiana Piscitelli1Angelica Petraroli2Roberta Parente3Maria Rosaria Galdiero4Gilda Varricchi5Giancarlo Marone6Massimo Triggiani7Vincenzo Di Marzo8Stefania Loffredo9Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, Naples, ItalyEndocannabinoid Research Group, Istituto di Chimica Biomolecolare-Consiglio Nazionale delle Ricerche (ICB-CNR), Pozzuoli, ItalyDepartment of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, Naples, ItalyDivision of Allergy and Clinical Immunology, University of Salerno, ItalyDepartment of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, Naples, ItalyDepartment of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, Naples, ItalyDepartment of Public Health, University of Naples Federico II, ItalyDivision of Allergy and Clinical Immunology, University of Salerno, ItalyEndocannabinoid Research Group, Istituto di Chimica Biomolecolare-Consiglio Nazionale delle Ricerche (ICB-CNR), Pozzuoli, ItalyDepartment of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, Naples, ItalyBackground. Mastocytosis is a condition characterized by the expansion and accumulation of mast cells (MCs) in various organs. The symptoms are related to the increased release of MC-derived mediators that exert local and distant effects. MCs are a source and target of phospholipase enzymes (PLs), which catalyze the cleavage of membrane phospholipids releasing lipid mediators (e.g., diacylglycerols (DAGs) and the endocannabinoid (EC) 2-arachidonoylglycerol (2-AG)). To date, there are no data on the role of these lipid mediators in mastocytosis. Here, we analyzed plasma levels of PLA2, PLC, DAG, ECs, and EC-related N-acylethanolamines in patients with mastocytosis. Methods. In 23 patients with mastocytosis and 23 healthy individuals, we measured plasma PLA2 and PLC activities, DAG, 2-AG, anandamide (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA). Results. Plasma PLA2 and PLC activities were increased in mastocytosis patients compared to controls. Concentrations of DAG (18:1 20:4 and 18:0 20:4), two second messengers produced by PLC, were higher in mastocytosis compared to controls, whereas the concentrations of their metabolite, 2-AG, were not altered. AEA was decreased in mastocytosis patients compared to controls; by contrast, AEA congener, PEA, was increased. PLA2 and PLC activities were increased only in patients with mediator-related symptoms. Moreover, PLC activity was positively correlated with disease severity and tryptase concentrations. By contrast, AEA was negatively correlated with tryptase concentrations. Conclusions. PLs and some lipid mediators are altered in patients with mastocytosis. Our results may pave the way for investigating the functions of these mediators in the pathophysiology of mastocytosis and provide new potential biomarkers and therapeutic targets.http://dx.doi.org/10.1155/2019/5836476
spellingShingle Anne Lise Ferrara
Fabiana Piscitelli
Angelica Petraroli
Roberta Parente
Maria Rosaria Galdiero
Gilda Varricchi
Giancarlo Marone
Massimo Triggiani
Vincenzo Di Marzo
Stefania Loffredo
Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients with Mastocytosis
Journal of Immunology Research
title Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients with Mastocytosis
title_full Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients with Mastocytosis
title_fullStr Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients with Mastocytosis
title_full_unstemmed Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients with Mastocytosis
title_short Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients with Mastocytosis
title_sort altered metabolism of phospholipases diacylglycerols endocannabinoids and n acylethanolamines in patients with mastocytosis
url http://dx.doi.org/10.1155/2019/5836476
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