期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 127, 期 5, 页码 1267-U282出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2010.12.1078
关键词
Mast cell; autophagy; CD63; degranulation; p62; light chain 3 (LC3)
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Japan Society for the Promotion of Science
- Promotion and Mutual Aid Corporation for Private Schools of Japan
- MEXT, Japan
- Takeda Science Foundation
- Astellas Foundation for Research on Metabolic Disorders
- Grants-in-Aid for Scientific Research [23590576, 23659404, 23390260] Funding Source: KAKEN
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 FceRI 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. (J Allergy Clin Immunol 2011;127:1267-76.)
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