Mechanisms for adhesion and leakage of pge_2-activated mast cells to and from extracellular matrix

在实验期间（2005-2006），我们取得了以下研究成果：1。PGE_2激活肥大细胞粘附机制的研究：PGE_2通过EP 4受体（cAMP-PKA）和EP 3受体（磷脂酶C-Ca_（2+）-钙调蛋白）信号通路促进小鼠肥大细胞与纤维连接蛋白的粘附。EP 4信号的最大反应出现在5-6 h，而EP 3信号的最大反应出现在15-16 h。结论：1.下游信号是通过肌苷激酶磷酸化-去磷酸化激活整合素。肥大细胞对纤维连接蛋白的渗漏机制研究：肥大细胞对纤维连接蛋白的渗漏始于PGE 2刺激后24 h，依赖于Epac诱导的Ca_（2+）动员的刺激，随后是钙调素的激活。3. PGE_2受体EP_4依赖的小鼠气囊腔周围皮下组织肥大细胞与基质成分的粘附：我们成功地建立了一种新的测量皮下组织中粘附肥大细胞数量的方法，并证明了EP_4受体而非EP_3受体在这种反应中的重要作用。

We obtained following research results during experiment period (2005-2006)1. A study for adhesion mechanism of PGE_2-activated mast cells: PGE_2 stimulated adhesion of mouse mast cells to plate-bound fibronectin through signaling of EP4 receptor (cAMP-PKA) and EP3 receptor (phospholipase C-Ca_<2+>-calmodulin). The maximum response of EP4 signaling appeared 5-6 h, but that of EP3 15-16 h after stimulation. Down stream signaling was found to be activation of integrin via myosine kinase phosphorylation-dephosphorylation.2. A study for leakage mechanism of mast cells adhered to fibronectin: The leakage of adhered mast cells to fibronectin, initiated 24 h after PGE2 stimulation, depended on a stimulation of Epac-induced Ca_<2+> mobilization and followed calmodulin activation..3. PGE_2-receptor EP4-dependent adherence of mast cells to matrix components in subcutaneous tissues around air pouch cavity of mice: We successed to develop a new method for measurement the number of adhered mast cells in subcutaneous tissues and demonstrated the important role of EP4 receptor but not EP3 receptor in the response.