Blockade of eosinophil migration by 5-lipoxygenase and cyclooxygenase inhibition in explanted guinea pig trachealis.

Blockade of eosinophil migration by 5-lipoxygenase and cyclooxygenase inhibition in explanted guinea pig trachealis.
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在外植的豚鼠气管中通过 5-脂氧合酶和环氧合酶抑制来阻断嗜酸性粒细胞迁移。

DOI:
10.1152/ajplung.1995.268.3.l446
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发表时间:
1995
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Leff,AR
Leff,AR
中科院分区:
--
文献类型:
--
作者:
Muñoz,NM;Leff,AR

文献摘要

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我们研究了用 A63162 抑制 5-脂氧合酶和用吲哚美辛 (INDO) 抑制环氧合酶对豚鼠气管外植体中 1) 嗜酸性粒细胞趋化性和 2) 10(-6) M 甲酰基-Met-Leu-Phe (fMLP) 引起的气道狭窄的影响。通过校准测微法评估气道狭窄,从固有层迁移的嗜酸性粒细胞表示为每 1 cm 气管段所含嗜酸性粒细胞的数量。 120 分钟后,fMLP 处理导致管腔嗜酸性粒细胞从 6,804 +/- 1,786 增加到 303,347 +/- 75,609 个细胞(P < 0.001);气道直径缩小 20.4 +/- 1.4%。在六种制剂中,A63162 抑制 fMLP 引起的气道狭窄达 54.9 +/- 6.1%; INDO 对气道直径也有类似的影响。然而,10(-6) M A63162 后对嗜酸性粒细胞迁移的最大抑制(38,393 +/- 7,434 个细胞;P < 0.001 与单独的 fMLP 相比)比用 10(-5) M INDO 处理后(123,547 +/- 19,499 个细胞;P < 0.05)更大。我们展示了一种方法,可以同时测量豚鼠气管外植体制备中的嗜酸性粒细胞迁移和气道平滑肌收缩。我们的数据表明,嗜酸性粒细胞趋化性和气道内径的变化是由 5-脂氧合酶和环氧合酶途径的激活引起的,并且细胞迁移与气道平滑肌收缩的物理后果无关。
We studied the effects of 5-lipoxygenase inhibition with A63162 and cyclooxygenase inhibition with indomethacin (INDO) on 1) eosinophil chemotaxis and 2) airway narrowing caused by 10(-6) M formyl-Met-Leu-Phe (fMLP) in tracheal explants from guinea pigs. Airway narrowing was assessed by calibrated micrometry, and eosinophil migration from the lamina propria was expressed as number of eosinophils contained per 1 cm tracheal segment. After 120 min, treatment with fMLP caused an increase in luminal eosinophils from 6,804 +/- 1,786 to 303,347 +/- 75,609 cells (P < 0.001); airway diameter narrowed by 20.4 +/- 1.4%. In six preparations, A63162 inhibited airway narrowing caused by fMLP by 54.9 +/- 6.1%; INDO had a similar effect on airway diameter. However, maximal inhibition of eosinophil migration was greater after 10(-6) M A63162 (38,393 +/- 7,434 cells; P < 0.001 vs. fMLP alone) than after treatment with 10(-5) M INDO (123,547 +/- 19,499 cells; P < 0.05). We demonstrate a method that permits simultaneous measurements of eosinophil migration and airway smooth muscle contraction in a guinea pig tracheal explant preparation. Our data suggest that eosinophil chemotaxis and changes in internal airway diameter are caused by activation of both 5-lipoxygenase and cyclooxygenase pathways and that cell migration is independent of the physical consequences of airway smooth muscle contraction.