Tryptase activates calcium-independent phospholipase A2 and releases PGE2 in airway epithelial cells.
Tryptase activates calcium-independent phospholipase A2 and releases PGE2 in airway epithelial cells.
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类胰蛋白酶激活不依赖钙的磷脂酶 A2 并在气道上皮细胞中释放 PGE2。
DOI：
10.1152/ajplung.90230.2008
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
McHowat,Jane
中科院分区：
文献类型：
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作者：
Rastogi,Prerna;Young,DawnM;McHowat,Jane
人类小气道上皮细胞(HSAEC)构成了外部环境过敏原和内部肺环境之间的边界。肥大细胞存在于散布在肺上皮内的人肺组织中，可从其颗粒中分泌大量新形成的和预先形成的介质，这些介质可能会传播小气道炎症。在本研究中，类胰蛋白酶刺激HSAEC增加了膜相关的非钙依赖性磷脂酶A2γ(iPLA2γ)的活性，导致花生四烯酸和PGE2的释放增加。用iPLA2选择性抑制剂溴烯醇内酯预处理HSAEC可抑制上述反应。环氧合酶(COX)-1选择性抑制剂SC-560和非选择性COX抑制剂阿司匹林可抑制类胰酶刺激的HSAEC产生PGE2，而COX-2选择性抑制剂CAY10404则不能抑制类胰酶刺激的HSAEC早期释放花生四烯酸，提示在类胰蛋白酶刺激的HSAEC中，花生四烯酸的早期释放是由结构性COX-1代谢形成PGE2。此外，血小板活化因子的产生和中性粒细胞对类胰蛋白酶刺激的HSAEC的黏附也增加。这种复杂的反应可以在小气道内产生一连串的炎性介质。我们推测，选择性抑制iPLA2γ介导的磷脂水解可能在炎症性呼吸道疾病中被证明是有益的。
Human small airway epithelial cells (HSAEC) form the boundary between the external environmental allergens and the internal lung milieu. Mast cells are present in human lung tissue interspersed within the pulmonary epithelium and can secrete a host of pre- and newly formed mediators from their granules, which may propagate small airway inflammation. In this study, tryptase stimulation of HSAEC increased membrane-associated, calcium-independent phospholipase A2γ (iPLA2γ) activity, resulting in increased arachidonic acid and PGE2release. These responses were inhibited by pretreating HSAEC with the iPLA2-selective inhibitor bromoenol lactone. The tryptase-stimulated PGE2production was inhibited by treating HSAEC with the cyclooxygenase (COX)-1-selective inhibitor SC-560 and the nonselective COX inhibitor aspirin but not by the COX-2-selective inhibitor CAY10404, indicating that the early release of arachidonic acid is metabolized by constitutive COX-1 to form PGE2in tryptase-stimulated HSAEC. Additionally, platelet-activating factor production and neutrophil adherence to tryptase-stimulated HSAEC was also increased. This complex response can set up a cascade of inflammatory mediator production in small airways. We speculate that selective inhibition of iPLA2γ-mediated phospholipid hydrolysis may prove beneficial in inflammatory airway diseases.