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J Allergy Clin Immunol. 2011 May;127(5):1267-76.e6. doi: 10.1016/j.jaci.2010.12.1078. Epub 2011 Feb 18.

Crucial role for autophagy in degranulation of mast cells.

Author information

1
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan. hushio@juntendo.ac.jp

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 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.

PMID:
21333342
DOI:
10.1016/j.jaci.2010.12.1078
[Indexed for MEDLINE]

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