Effect of mode of activation of human eosinophils on tracheal smooth muscle contraction in guinea pigs.
Effect of mode of activation of human eosinophils on tracheal smooth muscle contraction in guinea pigs.
复制标题
人嗜酸性粒细胞激活模式对豚鼠气管平滑肌收缩的影响。
DOI：
10.1152/ajplung.1993.264.5.l475
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Leff,AR
中科院分区：
文献类型：
--
作者：
Strek,ME;White,SR;Hsiue,TR;Kulp,GV;Williams,FS;Leff,AR
我们研究了离体人嗜酸性粒细胞的激活方式与豚鼠离体气管平滑肌（TSM）原位反应的关系。用10(-7)M肉豆酸酯phorbol acetate （PMA）或10(-6)M甲酰基-蛋氨酸-leucyl-苯丙氨酸(fMLP) + 5微克/毫升细胞松弛素B （CYB）激活人外周血嗜酸性粒细胞，并通过动力学法测定嗜酸性粒细胞过氧化物酶（EPO）的分泌来证实其活化作用。fMLP+CYB（占总嗜酸性粒细胞含量的10.2 +/- 3.2%）和PMA（占总含量的10.0 +/- 2.8%,P = NS）激活后EPO分泌相似。fMLP+CYB激活的6 × 10(6)个嗜酸性粒细胞/cm2局部应用于TSM节段，5种制剂的活性张力（AT）为0.51 +/- 0.14 g/cm（与基线相比P < 0.03）；经PMA活化的细胞无收缩反应（0.04 +/- 0.03 g/cm AT, P = NS vs基线）。PMA-和fMLP+ cyb活化细胞均可引起豚鼠气管毒蕈碱反应性增强。引起阈值反应（ED0.3）所需的静脉乙酰胆碱剂量基线为-7.3 +/- 0.1 log mol/kg，而fMLP+ cyb活化嗜酸性粒细胞治疗后为-8.7 +/- 0.5 log mol/kg (P = 0.05)，基线为-6.9 +/- 0.1 log mol/kg，而pma活化细胞治疗后为-7.5 +/- 0.1 log mol/kg （P < 0.01）。在用fMLP+CYB激活之前，用200 microM A-63162（5-脂氧合酶抑制剂）预处理嗜酸性粒细胞，可以阻断AT和增强的毒菌碱反应性。我们证明，被激活的嗜酸性粒细胞（通过EPO分泌来评估）通过分泌5-脂氧合酶途径的产物，导致豚鼠TSM增强毒蕈碱反应和/或直接收缩。（摘要删节250字）
We studied the relationship between mode of activation of isolated human eosinophils and in situ responsiveness in isolated tracheal smooth muscle (TSM) of guinea pigs. Human peripheral blood eosinophils were activated with either 10(-7) M phorbol myristate acetate (PMA) or 10(-6) M formyl-methionyl-leucyl-phenylalanine (fMLP) + 5 micrograms/ml cytochalasin B (CYB), and activation was confirmed by measurement of eosinophil peroxidase (EPO) secretion by kinetic assay. EPO secretion was similar after activation with fMLP+CYB (10.2 +/- 3.2% of total eosinophil content) and PMA (10.0 +/- 2.8% of total content; P = NS). Topical application of 6 x 10(6) eosinophils/cm2 activated with fMLP+CYB to the TSM segment caused 0.51 +/- 0.14 g/cm active tension (AT) in five preparations (P < 0.03 vs. baseline); cells activated with PMA caused no contractile response (0.04 +/- 0.03 g/cm AT, P = NS vs. baseline). Both PMA- and fMLP+CYB-activated cells caused augmentation of muscarinic responsiveness of guinea pig trachealis. The dose of intravenous acetylcholine required to cause a threshold response (ED0.3) was -7.3 +/- 0.1 log mol/kg at baseline vs. -8.7 +/- 0.5 log mol/kg after treatment with fMLP+CYB-activated eosinophils (P = 0.05) and -6.9 +/- 0.1 log mol/kg at baseline vs. -7.5 +/- 0.1 log mol/kg after PMA-activated cells (P < 0.01). Both AT and augmented muscarinic responsiveness were blocked by pretreating the eosinophils with 200 microM A-63162, an inhibitor of 5-lipoxygenase, before activation with fMLP+CYB. We demonstrate that eosinophils activated comparably (as assessed by EPO secretion) cause augmented muscarinic responsiveness and/or direct contraction of guinea pig TSM through secretion of a product of the 5-lipoxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS)