Crucial role for autophagy in degranulation of mast cells

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• 作者：Hiroko Ushio PhD^a ; ^{hushio@juntendo.ac.jp"" rel=""nofollow} ; 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 PhDⁱ ; Sachiko Komazawa-Sakon BD^d ; Franç ; ois 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 ; ^{hnakano@juntendo.ac.jp"" rel=""nofollow}
• 关键词：Mast cell ; autophagy ; CD63 ; degranulation ; p62 ; light chain 3 (LC3)
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：127
• 期：5
• 页码：1267-1276.e6
• 全文大小：2716 K

文摘

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.

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.