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

1.前列腺素E_2激活的肥大细胞黏附机制的研究：前列腺素E_2通过EP4受体(cAMP-PKA)和EP3受体(磷脂酶C-钙调素)信号通路促进小鼠肥大细胞与平板结合纤维连接蛋白的黏附。EP4信号的最大反应出现在刺激后5~6h，而EP3信号的最大反应出现在刺激后15~16h。结果1.下游信号转导途径是通过肌氨酸激酶的磷酸化-去磷酸化激活整合素。肥大细胞与纤维连接蛋白黏附的渗漏机制研究：黏附的肥大细胞对纤维连接蛋白的渗漏始于PGE2刺激后24 h，依赖于EPAC诱导的Ca~(2+)&Gt；动员，继而是钙调素的激活。小鼠气囊腔周围皮下组织中PGE_2受体EP4依赖的肥大细胞与基质成分的黏附：我们成功地建立了一种新的方法来测量皮下组织中黏附的肥大细胞的数量，并证实了EP4受体而不是EP3受体在这一反应中的重要作用。

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.