Nielsen V G, Webster R O
Immunopharmacology. 1987 Feb;13(1):61-71. doi: 10.1016/0162-3109(87)90027-0.
We have found that pretreatment of human neutrophils with ibuprofen (0.10-1.0 mg/ml) results in an irreversible, concentration-dependent inhibition of superoxide anion generation and release of lysosomal enzymes (myeloperoxidase, lysozyme) stimulated by the synthetic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), the complement fragment C5a, and to a lesser extent by serum opsonized zymosan. Inhibition of granule exocytosis and oxygen radical generation at ibuprofen concentrations less than 5 mg/ml was not due to drug cytotoxicity since release of the cytoplasmic enzyme lactate dehydrogenase was not affected by ibuprofen. In contrast to neutrophil responses mediated by C5a or FMLP, ibuprofen did not inhibit either enzyme release or superoxide anion generation by neutrophils stimulated with phorbol myristate acetate. Ibuprofen did not function as an oxygen radical scavenger in a cell-free system in which superoxide anion was generated by the aerobic action of xanthine oxidase on hypoxanthine. Ibuprofen also inhibited in a concentration-dependent fashion both directed migration (chemotaxis) and stimulated random migration (chemokinesis) of neutrophils exposed to either FMLP or C5a. Inhibition of neutrophil adherence to plastic surfaces and bovine pulmonary artery endothelial cells was equally effective when the neutrophils were treated with ibuprofen before stimulation with FMLP or phorbol myristate acetate. The inhibitory effects of ibuprofen pretreatment of neutrophils could not be overcome by addition of prostaglandins E1 or E2 (0.3-300 nM). These results demonstrate that ibuprofen is capable of suppressing many functions thought to be important in neutrophil-mediated acute pulmonary inflammatory processes. Results of these experiments further suggest that ibuprofen may inhibit neutrophil functions by acting on cellular components separate from membrane receptors or by blockade of cyclo-oxygenase products which may be involved in these neutrophil functions.
我们发现，用布洛芬（0.10 - 1.0毫克/毫升）对人中性粒细胞进行预处理，会导致超氧阴离子生成以及溶酶体酶（髓过氧化物酶、溶菌酶）释放受到不可逆的、浓度依赖性抑制，这些酶的释放是由合成肽N - 甲酰甲硫氨酰 - 亮氨酰 - 苯丙氨酸（FMLP）、补体片段C5a刺激引起的，血清调理酵母聚糖对其刺激作用较小。在布洛芬浓度低于5毫克/毫升时，颗粒胞吐作用和氧自由基生成受到抑制并非由于药物细胞毒性，因为细胞质酶乳酸脱氢酶的释放不受布洛芬影响。与由C5a或FMLP介导的中性粒细胞反应不同，布洛芬不会抑制佛波酯刺激的中性粒细胞的酶释放或超氧阴离子生成。在无细胞系统中，布洛芬不作为氧自由基清除剂，该系统中黄嘌呤氧化酶对次黄嘌呤的需氧作用产生超氧阴离子。布洛芬还以浓度依赖性方式抑制暴露于FMLP或C5a的中性粒细胞的定向迁移（趋化性）和刺激的随机迁移（化学增活现象）。当在FMLP或佛波酯刺激之前用布洛芬处理中性粒细胞时，对中性粒细胞黏附于塑料表面和牛肺动脉内皮细胞的抑制同样有效。添加前列腺素E1或E2（0.3 - 300纳摩尔）无法克服布洛芬预处理中性粒细胞的抑制作用。这些结果表明，布洛芬能够抑制许多被认为在中性粒细胞介导的急性肺部炎症过程中起重要作用的功能。这些实验结果进一步表明，布洛芬可能通过作用于与膜受体分离的细胞成分或通过阻断可能参与这些中性粒细胞功能的环氧化酶产物来抑制中性粒细胞功能。
