Cuong Dang Van, Kim Hyoung Kyu, Marquez Jubert, Kim Nari, Ko Kyung Soo, Rhee Byoung Doo, Han Jin
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.; Department of Integrated Biomedical Science, College of Medicine, Inje University, Busan 47392, Korea.
Korean J Physiol Pharmacol. 2016 Mar;20(2):213-20. doi: 10.4196/kjpp.2016.20.2.213. Epub 2016 Feb 23.
Mast cells are primary mediators of allergic inflammation. Beta-1,3-glucan (BG) protects against infection and shock by activating immune cells. Activation of the BG receptor induces an increase in intracellular Ca(2+), which may induce exocytosis. However, little is known about the precise mechanisms underlying BG activation of immune cells and the possible role of mitochondria in this process. The present study examined whether BG induced mast cell degranulation, and evaluated the role of calcium transients during mast cell activation. Our investigation focused on the role of the mitochondrial calcium uniporter (MCU) in BG-induced degranulation. Black mouse (C57) bone marrow-derived mast cells were stimulated with 0.5 µg/ml BG, 100 µg/ml peptidoglycan (PGN), or 10 µM A23187 (calcium ionophore), and dynamic changes in cytosolic and mitochondrial calcium and membrane potential were monitored. BG-induced mast cell degranulation occurred in a time-dependent manner, and was significantly reduced under calcium-free conditions. Ruthenium red, a mitochondrial Ca(2+) uniporter blocker, significantly reduced mast cell degranulation induced by BG, PGN, and A23187. These results suggest that the mitochondrial Ca(2+) uniporter has an important regulatory role in BG-induced mast cell degranulation.
肥大细胞是过敏性炎症的主要介质。β-1,3-葡聚糖（BG）通过激活免疫细胞来预防感染和休克。BG受体的激活会导致细胞内Ca(2+)增加，这可能会诱导胞吐作用。然而，关于BG激活免疫细胞的精确机制以及线粒体在此过程中可能发挥的作用，我们知之甚少。本研究检测了BG是否会诱导肥大细胞脱颗粒，并评估了钙瞬变在肥大细胞激活过程中的作用。我们的研究重点是线粒体钙单向转运体（MCU）在BG诱导的脱颗粒中的作用。用0.5μg/ml BG、100μg/ml肽聚糖（PGN）或10μM A23187（钙离子载体）刺激黑鼠（C57）骨髓来源的肥大细胞，并监测胞质和线粒体钙以及膜电位的动态变化。BG诱导的肥大细胞脱颗粒呈时间依赖性，且在无钙条件下显著减少。线粒体Ca(2+)单向转运体阻滞剂钌红显著降低了BG、PGN和A23187诱导的肥大细胞脱颗粒。这些结果表明，线粒体Ca(2+)单向转运体在BG诱导的肥大细胞脱颗粒中具有重要的调节作用。
