Adipose triglyceride lipase acts on neutrophil lipid droplets to regulate substrate availability for lipid mediator synthesis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: inflammatory cells;    arachidonic acid;    eicosanoids;    lipolysis;   

DOI  :  10.1189/jlb.3A0515-206R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inhumans,mutationsinATGLleadtoTGaccumulationinLDsofmosttissuesandcells,includingperipheralbloodleukocytes.ThispathologicconditioniscalledJordans’anomaly,inwhichfunctionalconsequenceshavenotbeeninvestigated.Inthepresentstudy,wetestedthehypothesisthatATGLplaysaroleinleukocyteLDmetabolismandimmunecellfunction.Similartohumanswithloss‐of‐functionmutationsinATGL,wefoundthatglobalandmyeloid‐specificAtgl−/−miceexhibitJordans’anomalywithincreasedabundanceofintracellularTG‐richLDsinneutrophilgranulocytes.Inamodelofinflammatoryperitonitis,lipidaccumulationwasalsoobservedinmonocytesandmacrophagesbutnotineosinophilsorlymphocytes.NeutrophilsfromAtgl−/−miceshowedenhancedimmuneresponsesinvitro,whichweremoreprominentincellsfromglobalcomparedwithmyeloid‐specificAtgl−/−mice.Mechanistically,ATGL−/−aswellaspharmacologicalinhibitionofATGLledtoanimpairedreleaseoflipidmediatorsfromneutrophils.ThesefindingsdemonstratethatthereleaseoflipidmediatorsisdependentontheliberationofprecursormoleculesfromtheTG‐richpoolofLDsbyATGL.OurdataprovidemechanisticinsightsintoJordans’anomalyinneutrophilsandsuggestthatATGLisapotentregulatorofimmunecellfunctionandinflammatorydiseases...

【 授权许可】

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