Anderson R, Lukey P T, van Rensburg C E
Agents Actions. 1985 Sep;16(6):527-34. doi: 10.1007/BF01983658.
Benoxaprofen was previously found to inhibit the random and leucoattractant-induced migration of human polymorphonuclear leucocytes in vitro by a pro-oxidative mechanism [1]. In this study the effects of benoxaprofen on the binding to PMNL of the synthetic chemotactic tripeptide FMLP, on the oxidative inactivation of this leucoattractant by PMNL and on PMNL chemotaxis, chemokinesis and orientation in an FMLP gradient have been investigated. At concentrations of 10(-5) M (3 micrograms/ml) benoxaprofen inhibited PMNL random and leucoattractant-induced migration and increased PMNL membrane-associated oxidative metabolism and cellular auto-oxidation. These effects of benoxaprofen on PMNL migration and auto-oxidation were prevented by the anti-oxidant cysteine (10(-3) M). Benoxaprofen inhibited both FMLP-induced chemotaxis and chemokinesis but did not affect the binding of radiolabelled FMLP to PMNL or orientation of the cells in a positive gradient of the leucoattractant. Benoxaprofen at concentrations of 5 X 10(-5) M significantly increased the oxidative inactivation of FMLP by PMNL. Inhibition of PMNL migration by benoxaprofen is mediated by the two different pro-oxidative mechanisms, viz. a cell-directed auto-oxidative mechanism and potentiation of the oxidative inactivation of leucoattractants by PMNL.
先前发现苯恶洛芬在体外通过一种促氧化机制抑制人多形核白细胞的随机迁移以及白三烯诱导的迁移[1]。在本研究中，已对苯恶洛芬对合成趋化三肽FMLP与多形核白细胞（PMNL）结合的影响、PMNL对这种白三烯趋化剂的氧化失活作用以及对PMNL趋化性、趋化运动和在FMLP梯度中的定向作用进行了研究。在浓度为10(-5)M（3微克/毫升）时，苯恶洛芬抑制PMNL的随机迁移和白三烯趋化剂诱导的迁移，并增加PMNL膜相关的氧化代谢和细胞自氧化。抗氧化剂半胱氨酸（10(-3)M）可阻止苯恶洛芬对PMNL迁移和自氧化的这些作用。苯恶洛芬抑制FMLP诱导的趋化性和趋化运动，但不影响放射性标记的FMLP与PMNL的结合或细胞在白三烯趋化剂正梯度中的定向。浓度为5×10(-5)M的苯恶洛芬显著增加PMNL对FMLP的氧化失活。苯恶洛芬对PMNL迁移的抑制作用是由两种不同的促氧化机制介导的，即细胞定向的自氧化机制和PMNL对白三烯趋化剂氧化失活的增强作用。
