Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
Autophagy. 2011 Jun;7(6):657-9. doi: 10.4161/auto.7.6.15384. Epub 2011 Jun 1.
Mast cells play a crucial role in allergic inflammatory reactions through releasing cytosolic granules upon antigen stimulation. However, the mechanisms underlying maturation and release of secretory granules are not fully understood. We found that autophagy is constitutively induced in mast cells under full nutrition conditions, and type II LC3 (LC3-II), a marker for autophagosomes, localizes on secretory granules. While deletion of Atg7 does not impair the development of bone marrow-derived mast cells (BMMCs), Atg7-deficient BMMCs show severe impairment of degranulation, but not cytokine production, upon antigen stimulation. Moreover we found that LC3-II, but not LC3-I, colocalizes with CD63, a marker for secretory lysosomes and is released extracellularly along with degranulation in wild-type BMMCs, but not Atg7-deficient BMMCs. Finally, passive cutaneous anaphylaxis reactions are almost completely abolished in mast celldeficient mice reconstituted with Atg7-deficient BMMCs. Collectively, these results suggest that autophagy is not essential for the development, but plays a crucial role in degranulation, of mast cells.
肥大细胞通过在抗原刺激下释放胞质颗粒在过敏炎症反应中发挥关键作用。然而，分泌颗粒成熟和释放的机制尚未完全阐明。我们发现，在完全营养条件下，肥大细胞中持续诱导自噬，并且自噬体的标志物 II 型 LC3（LC3-II）定位于分泌颗粒上。虽然 Atg7 的缺失不会损害骨髓来源的肥大细胞（BMMC）的发育，但 Atg7 缺陷型 BMMC 在抗原刺激下严重损害脱颗粒，但不影响细胞因子产生。此外，我们发现 LC3-II，而不是 LC3-I，与 CD63 共定位，CD63 是分泌溶酶体的标志物，并且在野生型 BMMC 中与脱颗粒一起释放到细胞外，但在 Atg7 缺陷型 BMMC 中则不然。最后，用 Atg7 缺陷型 BMMC 重建的肥大细胞缺陷小鼠的皮肤被动过敏反应几乎完全被消除。总之，这些结果表明自噬对于肥大细胞的发育不是必需的，但在脱颗粒中起着至关重要的作用。
