Crucial role for autophagy in degranulation of mast cells - 11/08/11
, Takashi Ueno, PhD b, Yuko Kojima, PhD c, Masaaki Komatsu, PhD e, f, Satoshi Tanaka, PhD g, Akitsugu Yamamoto, PhD h, Yoshinobu Ichimura, PhD e, Junji Ezaki, PhD b, Keigo Nishida, PhD i, Sachiko Komazawa-Sakon, BD d, François Niyonsaba, PhD a, Tetsuro Ishii, PhD j, Toru Yanagawa, DDS, MD, PhD j, Eiki Kominami, MD, PhD b, Hideoki Ogawa, MD, PhD a, Ko Okumura, MD, PhD a, d, Hiroyasu Nakano, MD, PhD d, ⁎ 
Reprint requests: Hiroko Ushio, PhD, or Hiroyasu Nakano, MD, PhD, Atopy Research Center or Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.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/WV mice reconstituted with Atg7-/- BMMCs compared with Atg7+/+ BMMCs.
Conclusion |
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.
El texto completo de este artículo está disponible en PDF.Key words : Mast cell, autophagy, CD63, degranulation, p62, light chain 3 (LC3)
Abbreviations used : Atg, BM, BMMC, DC, FcεRI, GM-CSF, GFP, LC3, LC3-I, LC3-II, LTC4, M-CSF, MFI, MVBs, PCA, PMA, Poly I:C, SCF, siRNA, SNARE
Esquema
| Supported in part by grants-in-aid for the “High-Tech Research Center” Project for Private Universities; a matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and Scientific Research (B) and (C) from the Japan Society for the Promotion of Science; the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan; Scientific Research on Innovative Areas; MEXT, Japan; the Takeda Science Foundation; and the Astellas Foundation for Research on Metabolic Disorders. |
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| Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 127 - N° 5
P. 1267 - mai 2011 Regresar al número
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