title: Crucial role for autophagy in degranulation of mast cells.
abstract: BACKGROUND
  Autophagy plays a crucial role in controlling various biological responses including starvation, homeostatic turnover of long-lived proteins, and invasion of bacteria. However, a role for autophagy in development and/or function of mast cells is unknown.
  
  
  OBJECTIVE
  To investigate a role for autophagy in mast cells, we generated bone marrow-derived mast cells (BMMCs) from mice lacking autophagy related gene (Atg) 7, an essential enzyme for autophagy induction.
  
  
  METHODS
  Bone marrow-derived mast cells were generated from bone marrow cells of control and IFN-inducible Atg7-deficient mice, and morphologic and functional analyses were performed.
  
  
  RESULTS
  We found that conversion of type I to type II light chain (LC3)-II, a hallmark of autophagy, was constitutively induced in mast cells under full nutrient conditions, and LC3-II localized in secretory granules of mast cells. Although deletion of Atg7 did not impair the development of BMMCs, Atg7(-/-) BMMCs showed severe impairment of degranulation, but not cytokine production on FcεRI cross-linking. Intriguingly, LC3-II but not LC3-I was co-localized with CD63, a secretory lysosomal marker, and was released extracellularly along with degranulation in Atg7(+/+) but not Atg7(-/-) BMMCs. Moreover, passive cutaneous anaphylaxis reactions were severely impaired in mast cell-deficient WBB6F1-W/W(V) mice reconstituted with Atg7(-/-) BMMCs compared with Atg7(+/+) BMMCs.
  
  
  CONCLUSIONS
  These results suggest that autophagy is not essential for the development but plays a crucial role in degranulation of mast cells. Thus, autophagy might be a potential target to treat allergic diseases in which mast cells are critically involved.
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan. hushio@juntendo.ac.jp
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ushio
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueno
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kojima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ichimura
authors.forename: Junji
authors.initials: J
authors.lastname: Ezaki
authors.forename: Keigo
authors.initials: K
authors.lastname: Nishida
authors.forename: Sachiko
authors.initials: S
authors.lastname: Komazawa-Sakon
authors.forename: François
authors.initials: F
authors.lastname: Niyonsaba
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishii
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Eiki
authors.initials: E
authors.lastname: Kominami
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakano
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D015550:Cell Degranulation / Q000502:physiology*; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D060149:Tetraspanin 30
chemical_list: D015703:Antigens, CD; C502661:Atg7 protein, mouse; C554586:CD63 protein, human; C554587:Cd63 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D000071193:Autophagy-Related Protein 7