Hisada T, Salmon M, Nasuhara Y, Chung K F
Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Am J Respir Crit Care Med. 1999 Aug;160(2):571-5. doi: 10.1164/ajrccm.160.2.9810101.
Eotaxin, a selective chemoattractant for eosinophils, induces lung eosinophilia and bronchial hyperresponsiveness (BHR) when administered intratracheally to interleukin-5 (IL-5) transgenic mice. We determined whether these effects of eotaxin were mediated through the production of cysteinyl-leukotrienes. IL-5 transgenic mice were administered eotaxin (5 micrograms) intratracheally after pretreatment with either diluent or a selective 5-lipoxygenase inhibitor SB210661 or a cysteinyl-leukotriene receptor antagonist, pranlukast. Twenty-four hours later, bronchial responsiveness to acetylcholine was measured and the degree of eosinophil influx was determined in bronchoalveolar lavage fluid (BALF) or in lung tissue. Both pranlukast and SB210661 significantly attenuated BHR induced by eotaxin with logPC(50), which is the concentration of acetylcholine needed to increase baseline insufflation pressure by 50%, from -0.43 +/- 0.16 to 0.39 +/- 0.10 and from -0.22 +/- 0.10 to 0.53 +/- 0.10, respectively (p < 0.05). There was also a significant attenuation of the eosinophil counts in BALF and in airways. BALF levels of leukotriene C(4) (LTC(4)) showed a significant increase after eotaxin from 23.9 +/- 6.7 to 165.0 +/- 35.0 pg/ml (p < 0.05) but were partially suppressed by both SB210661 (71.2 +/- 21.0) and pranlukast (62.7 +/- 11.5). Concentrations of LTB(4) were not significantly changed. We conclude that eotaxin-induced effects in the airways of IL-5 transgenic mice are partly mediated by the activation of 5-lipoxygenase enzyme leading to the generation of cysteinyl-leukotrienes.
嗜酸性粒细胞趋化因子是一种对嗜酸性粒细胞具有选择性的趋化因子，当经气管内给予白细胞介素-5（IL-5）转基因小鼠时，可诱导肺部嗜酸性粒细胞增多和支气管高反应性（BHR）。我们确定了嗜酸性粒细胞趋化因子的这些作用是否通过半胱氨酰白三烯的产生介导。在用稀释剂或选择性5-脂氧合酶抑制剂SB210661或半胱氨酰白三烯受体拮抗剂普仑司特预处理后，经气管内给予IL-5转基因小鼠嗜酸性粒细胞趋化因子（5微克）。24小时后，测量支气管对乙酰胆碱的反应性，并测定支气管肺泡灌洗液（BALF）或肺组织中嗜酸性粒细胞流入的程度。普仑司特和SB210661均显著减轻了嗜酸性粒细胞趋化因子诱导的BHR，使logPC(50)（即使基线吹入压力增加50%所需的乙酰胆碱浓度）分别从-0.43±0.16变为0.39±0.10和从-0.22±0.10变为0.53±0.10（p<0.05）。BALF和气道中的嗜酸性粒细胞计数也显著减少。嗜酸性粒细胞趋化因子作用后，BALF中白三烯C(4)（LTC(4)）水平从23.9±6.7显著增加至165.0±35.0 pg/ml（p<0.05），但均被SB210661（71.2±21.0）和普仑司特（62.7±11.5）部分抑制。白三烯B(4)的浓度无显著变化。我们得出结论，嗜酸性粒细胞趋化因子在IL-5转基因小鼠气道中诱导的作用部分是由5-脂氧合酶的激活介导的，导致半胱氨酰白三烯的生成。
