Chai Ok Hee, Han Eui-Hyeog, Choi Yun Ho, Kim Suhn Hee, Kim Hyoung Tae, Galli Stephen J, Song Chang Ho
Department of Anatomy, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
Regul Pept. 2011 Feb 25;167(1):79-85. doi: 10.1016/j.regpep.2010.11.005. Epub 2010 Dec 2.
Atrial natriuretic peptide (ANP) is widely distributed throughout the heart, skin, gastrointestinal and genital tracts, and nervous and immune systems. ANP acts to mediate vasodilation and induces mast cell activation in both human and rats in vitro. However, the mechanisms of ANP-induced mast cell activation, the extent to which ANP can induce tissue swelling, mast cell degranulation, and granulocyte infiltration in mouse skin are not fully understood. This issue was investigated by treatment with ANP in rat peritoneal mast cells (RPMCs) and mouse peritoneal mast cells (MPMCs) in vitro and by injection of ANP into the skin of congenic normal WBB6F1/J-Kit+/Kit+ +/+, genetically mast cell-deficient WBB6F1/J-Kit(W)/Kit(W-v) (W/W(v)) and mast cell-engrafted W/W(v) (BMCMC→W/W(v)) mice in vivo. ANP induced the release of histamine and TNF-α from RPMCs and enhanced serotonin release from MPMCs, in a dose-dependent fashion, as well as reduced cAMP level of RPMCs in vitro. In +/+ mice, ANP induced significant tissue swelling, mast cell degranulation, and granulocyte infiltration in a dose-dependent manner, whereas not in genetically mast cell-deficient W/W(v) mice. However, ANP-induced cutaneous inflammation has been restored in BMCMC→W/W(v) mice. These data indicate that mast cells play a key role in the ANP-induced cutaneous inflammation.
心房利钠肽（ANP）广泛分布于心脏、皮肤、胃肠道和生殖道以及神经和免疫系统。在体外，ANP对人和大鼠均有介导血管舒张及诱导肥大细胞活化的作用。然而，ANP诱导肥大细胞活化的机制，以及ANP在小鼠皮肤中诱导组织肿胀、肥大细胞脱颗粒和粒细胞浸润的程度尚不完全清楚。本研究通过体外培养大鼠腹膜肥大细胞（RPMCs）和小鼠腹膜肥大细胞（MPMCs）并用ANP处理，以及体内向同基因正常WBB6F1/J-Kit+/Kit+ +/+、遗传性肥大细胞缺陷型WBB6F1/J-Kit(W)/Kit(W-v) （W/W(v)）和肥大细胞植入型W/W(v) （BMCMC→W/W(v)）小鼠皮肤注射ANP来进行探究。体外实验中，ANP以剂量依赖的方式诱导RPMCs释放组胺和TNF-α，增强MPMCs释放5-羟色胺，并降低RPMCs的cAMP水平。在+/+小鼠中，ANP以剂量依赖的方式诱导显著组织肿胀、肥大细胞脱颗粒和粒细胞浸润，而在遗传性肥大细胞缺陷型W/W(v)小鼠中则无此现象。然而，在BMCMC→W/W(v)小鼠中，ANP诱导的皮肤炎症得以恢复。这些数据表明肥大细胞在ANP诱导的皮肤炎症中起关键作用。
