Studies of Phospholipase A2 as a new target for treatment of bronchial asthma

胞浆磷脂酶A2(PLA2)是细胞膜磷脂转化为花生四烯酸(AA)和溶血磷脂的限速酶，这些磷脂很容易代谢成白三烯、血栓素和血小板活化因子等炎症介质。白三烯受体拮抗剂或曲索黄烷受体拮抗剂已被认为是治疗哮喘的有效药物。因此，抑制cPLA2可能比使用白三烯或Thronboxane受体拮抗剂治疗哮喘更有效。我们先前报道，cPLA2调节人嗜酸性粒细胞与ICAM-1或VCAM-1的黏附，抑制cPLA2可阻断嗜酸性粒细胞向肺组织的迁移和抗原诱导的气道高反应性。在本研究中，我们研究了哮喘患者嗜酸性粒细胞中cPLA2的活性和定量是否比健康献血者更多。哮喘患者1-M FMLP的AA释放和cPLA2活性均显著高于健康献血者。正常人和哮喘患者cPLA2的定量分别为0.36±0.13 ng/10^6细胞和0.52±0.17 ng/10^6细胞(p=0.0285)。

Cytosolic phospholipase A_2 (PLA_2) is the rate-limiting enzyme involved in the conversion of membrane phospholipids to arachidonic acid (AA) and lysophospholipids, which are readily metabolized to inflammatory mediators such as leukotrienes, thromboxane and platelet-activation factor. It has been recognized that receptor antagonists of leukotrienes or thronboxane are effective for treatment of bronchial asthma. To inhibit cPLA2 thus might be more effective than using leukotrienes or thronboxane receptor antagonist on treatment of bronchial asthma. We previously reported that cPLA2 regulates adhesion of human eosinophils to ICAM-1 or VCAM-1, and that inhibition of cPLA2 blocked eosinophil migration to lung tissue and antigen-induced airway hyperresponsiveness. In this study we investigated whether activity and quantitatition of cPLA2 in eosinophils from patients with asthma is more excessive than its from healthy donors.Both AA release and cPLA2 activity from patients with asthma by 1□M FMLP were greater than its from healthy donors significantly. Quantitation of cPLA2 is 0.36±0.13 ng/10^6 cells from healthy donors and 0.52±0.17 ng/10^6 cells from patients with asthma(p=0.0285)