{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Johnson JL"],"funding":["NIDDK NIH HHS","Cystinosis Research Foundation","NHLBI NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","NIAMS NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["5529"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9492659"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Dysregulated secretion in neutrophil leukocytes associates with human inflammatory disease. The exocytosis response to triggering stimuli is sequential; gelatinase granules modulate the initiation of the innate immune response, followed by the release of pro-inflammatory azurophilic granules, requiring stronger stimulation. Exocytosis requires actin depolymerization which is actively counteracted under non-stimulatory conditions. Here we show that the actin nucleator, WASH, is necessary to maintain azurophilic granules in their refractory state by granule actin entrapment and interference with the Rab27a-JFC1 exocytic machinery. On the contrary, gelatinase granules of WASH-deficient neutrophil leukocytes are characterized by decreased Rac1, shortened granule-associated actin comets and imp"],"journal":["Nature communications"],"pubmed_title":["Differential dysregulation of granule subsets in WASH-deficient neutrophil leukocytes resulting in inflammation."],"pmcid":["PMC9492659"],"funding_grant_id":["R01AR070837","R01 AR070837","P01HL152958","CRFS2020-001","P01 HL152958","R01DK110162","R01 HL088256","R01HL088256","R01 DK110162"],"pubmed_authors":["Wineinger N","Johnson JL","Rahman F","Zhang J","Carvalho Gontijo R","Kiosses WB","Billadeau DD","Meneses-Salas E","Monfregola J","Yu J","Ursini MV","Hedrick CC","Ramadass M","Allen D","Chen D","Catz SD","Askari K","Zhu YP","Osborne DG","Grinstein S","Henderson SC","Pestonjamasp K"],"additional_accession":[]},"is_claimable":false,"name":"Differential dysregulation of granule subsets in WASH-deficient neutrophil leukocytes resulting in inflammation.","description":"Dysregulated secretion in neutrophil leukocytes associates with human inflammatory disease. The exocytosis response to triggering stimuli is sequential; gelatinase granules modulate the initiation of the innate immune response, followed by the release of pro-inflammatory azurophilic granules, requiring stronger stimulation. Exocytosis requires actin depolymerization which is actively counteracted under non-stimulatory conditions. Here we show that the actin nucleator, WASH, is necessary to maintain azurophilic granules in their refractory state by granule actin entrapment and interference with the Rab27a-JFC1 exocytic machinery. On the contrary, gelatinase granules of WASH-deficient neutrophil leukocytes are characterized by decreased Rac1, shortened granule-associated actin comets and imp","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-07-14T15:49:28.363Z","creation":"2025-04-04T09:30:02.244Z"},"accession":"S-EPMC9492659","cross_references":{"pubmed":["36130971"],"doi":["10.1038/s41467-022-33230-y"]}}