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Crucial role for autophagy in degranulation of mast cells

Ushio, Hiroko, Ueno, Takashi, Kojima, Yuko, Komatsu, Masaaki, Tanaka, Satoshi, Yamamoto, Akitsugu, Ichimura, Yoshinobu, Ezaki, Junji, Nishida, Keigo, Komazawa-Sakon, Sachiko, Niyonsaba, François, Ishii, Tetsuro, Yanagawa, Toru, Kominami, Eiki, Ogawa, Hideoki, Okumura, Ko, Nakano, Hiroyasu·2011·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2010.12.1078
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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. Conclusion These results suggest that autophagy is not essentia…

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Metadata

Authors
Ushio, H., Ueno, T., Kojima, Y., Komatsu, M., Tanaka, S., Yamamoto, A., Ichimura, Y., Ezaki, J., Nishida, K., Komazawa-Sakon, S., Niyonsaba, F., Ishii, T., Yanagawa, T., Kominami, E., Ogawa, H., Okumura, K., & Nakano, H.
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2011-05
Volume
127
Issue
5
Pages
1267-1276.e6
ISSN
0091-6749
DOI
10.1016/j.jaci.2010.12.1078
Cited by
124
References
6
Language
en
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CoChat. (2026). Citation check: Crucial role for autophagy in degranulation of mast cells. https://app.cochat.ai/papers/10.1016/j.jaci.2010.12.1078
The paper
Ushio, H., Ueno, T., Kojima, Y., Komatsu, M., Tanaka, S., Yamamoto, A., Ichimura, Y., Ezaki, J., Nishida, K., Komazawa-Sakon, S., Niyonsaba, F., Ishii, T., Yanagawa, T., Kominami, E., Ogawa, H., Okumura, K., & Nakano, H. (2011). Crucial role for autophagy in degranulation of mast cells. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2010.12.1078