Lipopolysaccharide-induced goblet cell hypersecretion in the guinea pig trachea: Inhibition by macrolides

Lipopolysaccharide-induced goblet cell hypersecretion in the guinea pig trachea: Inhibition by macrolides
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DOI:
10.1152/ajplung.1997.272.1.l15
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发表时间:
1997-01-01
影响因子:
4.9
通讯作者:
Konno, K
Konno, K
中科院分区:
医学2区
文献类型:
--
作者:
Tamaoki, J;Takeyama, K;Konno, K

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我们研究了大环内酯类对脂多糖诱导的豚鼠气管杯状细胞分泌的影响。在阿利新蓝和周期性酸希夫染色的气管粘膜组织学切片上,通过任意测定粘液评分来评估杯状细胞的分泌情况,粘液评分与粘液排出量呈负相关。吸入大肠杆菌LPS (5 mg/kg)可引起黏液评分的时间依赖性下降,3 h后最大反应从542 +/- 49降至92 +/- 20任意单位(P < 0.001),并伴有气管粘膜中性粒细胞数量的增加。口服克拉霉素和红霉素(5和10 mg/kg)对lps诱导的粘液排出具有剂量依赖性,而阿莫西林和头孢克洛对lps诱导的粘液排出没有影响。每一剂量的克拉霉素和红霉素,但不是阿莫西林或头孢克洛,同样减弱了lps诱导的中性粒细胞募集。这些结果表明,LPS刺激杯状细胞分泌和中性粒细胞在气道中的积累,大环内酯类可能对防止中性粒细胞相关的气道高分泌有价值。
We studied the effects of macrolides on lipopolysaccharide (LPS)-induced airway goblet cell secretion in the guinea pig trachea. The goblet cell secretion was assessed in histological sections of the tracheal mucosa stained with alcian blue and periodic acid Schiff by arbitrarily determining mucus score, which is inversely related to the magnitude of mucus discharge. Inhalation of Eschericha coli LPS (5 mg/kg) caused a time-dependent decrease in mucus score, with the maximal response being from 542 +/- 49 to 92 +/- 20 arbitrary units (P < 0.001) after 3 h, which was accompanied by an increase in the number of neutrophils in the tracheal mucosa. The LPS-induced mucus discharge was inhibited by oral clarithromycin and erythromycin in a dose-dependent manner (5 and 10 mg/kg), whereas amoxicillin and cefaclor had no effect. Each dose of clarithromycin and erythromycin, but not amoxicillin or cefaclor, likewise attenuated the LPS-induced recruitment of neutrophils. These results suggest that LPS stimulates goblet cell secretion and neutrophil accumulation in the airways and that macrolides may be of value in protecting against neutrophil-associated airway hypersecretion.