title: An unexpected role for autophagy in degranulation of mast cells.
abstract: Mast cells play a crucial role in allergic inflammatory reactions through releasing cytosolic granules upon antigen stimulation. However, the mechanisms underlying maturation and release of secretory granules are not fully understood. We found that autophagy is constitutively induced in mast cells under full nutrition conditions, and type II LC3 (LC3-II), a marker for autophagosomes, localizes on secretory granules. While deletion of Atg7 does not impair the development of bone marrow-derived mast cells (BMMCs), Atg7-deficient BMMCs show severe impairment of degranulation, but not cytokine production, upon antigen stimulation. Moreover we found that LC3-II, but not LC3-I, colocalizes with CD63, a marker for secretory lysosomes and is released extracellularly along with degranulation in wild-type BMMCs, but not Atg7-deficient BMMCs. Finally, passive cutaneous anaphylaxis reactions are almost completely abolished in mast celldeficient mice reconstituted with Atg7-deficient BMMCs. Collectively, these results suggest that autophagy is not essential for the development, but plays a crucial role in degranulation, of mast cells.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan. hnakano@juntendo.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakano
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ushio
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D001854:Bone Marrow Cells / Q000166:cytology*; D015550:Cell Degranulation / Q000276:immunology*; D006967:Hypersensitivity / Q000473:pathology; D007249:Inflammation; D007790:Lactosylceramides / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D010588:Phagosomes / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D060149:Tetraspanin 30
chemical_list: D015703:Antigens, CD; C502661:Atg7 protein, mouse; C554587:Cd63 protein, mouse; D007790:Lactosylceramides; D008869:Microtubule-Associated Proteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; C025575:lactotriaosylceramide; D000071193:Autophagy-Related Protein 7