Stretch of Atrial Myocytes Stimulates Recruitment of Macrophages via ATP Released Through Gap-Junction Channels
Stretch of Atrial Myocytes Stimulates Recruitment of Macrophages via ATP Released Through Gap-Junction Channels
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DOI：
10.1254/jphs.12202fp
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发表时间：
2012-12-01
影响因子：
3.5
通讯作者：
Furukawa, Tetsushi
中科院分区：
文献类型：
--
作者：
Oishi, Sakiko;Sasano, Tetsuo;Furukawa, Tetsushi
心房炎症对房颤的发生和发展至关重要。虽然左心房扩张是房颤的危险因素，但心房扩张与炎症的机制尚不清楚。我们评估了心房肌细胞牵张诱导巨噬细胞浸润的机制。将小鼠巨噬细胞与HL-1小鼠心房肌细胞衍生的细胞共培养。机械牵张作用于心房肌细胞诱导巨噬细胞迁移。差距连接通道阻断剂甘珀酸和非特异性ATP信号调节剂腺苷三磷酸双磷酸酶和磷酸吡哆醛-6-偶氮苯-2 '，4'-二磺酸盐抑制增强的迁移。机械牵张可引起心房肌细胞外ATP浓度一过性升高，甘珀酸可抑制这种升高。siRNA敲低泛连接蛋白-2抑制ATP释放和巨噬细胞迁移。小鼠接受横向主动脉缩窄或假手术。横主动脉缩窄术诱导巨噬细胞浸润。每日给予甘珀酸显著抑制心房中的巨噬细胞浸润。因此，机械拉伸心房肌细胞诱导巨噬细胞迁移的ATP通过间隙连接通道释放，至少部分，在体外。施用间隙连接家族通道阻断剂抑制了体内的这种炎症变化。
Atrial inflammation is critical to atrial fibrillation initiation and progression. Although left atrial dilatation is a risk factor for atrial fibrillation, the mechanism linking atrial dilatation and inflammation is unclear. We evaluated the mechanisms underlying infiltration of macrophages induced by stretch of atrial myocytes. Murine macrophages were co-cultured with HL-1 murine atrial myocyte derived cells. Mechanical stretch applied to atrial myocytes induced transwell macrophage migration. The gap junction channel blocker carbenoxolone and the non-specific ATP-signaling modifiers apyrase and pyridoxal-phosphate-6-azopheny1-2',4'-disulfonate inhibited the enhanced migration. Mechanical stretch of atrial myocytes induced transient increase in extracellular ATP concentration, which was inhibited by carbenoxolone. siRNA knockdown of pannexin-2 inhibited ATP release and macrophage migration. Mice underwent transverse aortic constriction or sham procedure. Transverse aortic constriction procedure induced macrophage infiltration. Daily carbenoxolone administration significantly inhibited macrophage infiltration in the atrium. Thus, mechanical stretch of atrial myocytes induces macrophage migration by ATP released through gap-junction channels, at least in part, in vitro. Administering a gap junction family channel blocker inhibited this inflammatory change in vivo.