Lipopolysaccharide Induces Mucus Cell Metaplasia in Mouse Lung.
Lipopolysaccharide Induces Mucus Cell Metaplasia in Mouse Lung.
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脂多糖诱导小鼠肺粘液细胞化生。
DOI：
10.1165/ajrcmb.24.1.4122
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Cheng,PW
中科院分区：
文献类型：
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作者：
Yanagihara,K;Seki,M;Cheng,PW
一种脂多糖（LPS）诱导的气道炎症和上皮细胞表型变化的小鼠模型，以及这些事件的时间过程进行了描述。通过支气管肺泡灌洗液中炎性细胞的分类细胞计数和苏木精和伊红（H&E）染色肺切片的组织学评估，单次肺内滴注铜绿假单胞菌LPS导致治疗后2天大量中性粒细胞向肺募集。LPS诱导的嗜酸性炎症在第4天基本消退，到第7天基本消失。直到LPS处理后第4天，通过Alcian蓝高碘酸-Schiff染色才检测到气道上皮粘液细胞，并且在第7天在数量和粘液含量上变得更丰富。Muc 5ac信使RNA（mRNA）以及糖蛋白的表达在第2天增强，在第4天达到峰值，并在第7天降低，而粘蛋白核心2 β 6 N-乙酰葡糖胺转移酶（C2 GnT）-M mRNA的表达增强直到第4天才检测到，并在第7天达到峰值。肺中C2 GnT-L mRNA（活化白细胞以及粘液细胞的标志物）的表达在第2天达到峰值，并保持中等高水平直至第7天。 C2 GnT-L mRNA在LPS处理的肺中的表达与中性粒细胞的存在和气道上皮中粘液细胞的出现相关。我们的结论是，粘液细胞化生和增生可以产生在小鼠肺内滴注LPS的一个单一的。此外，C2 GnT-M可以作为小鼠肺中粘液细胞的标志物。本模型可用于假单胞菌诱导的气道粘液高分泌性疾病的研究。
A murine model of lipopolysaccharide (LPS)-induced airway inflammation and epithelial cell phenotypic change, and the time courses of these events are described. A single intratracheal instillation ofPseudomonas aeruginosaLPS in mice resulted in massive recruitment of neutrophils to the lung 2 d after treatment as assessed by differential cell counts of the inflammatory cells in bronchoalveolar lavage fluid and histologic assessment of hemotoxylin and eosin (H&E)-stained lung sections. The LPS-induced neutrophilic inflammation subsided substantially on Day 4 and essentially vanished by Day 7. Airway epithelial mucus cells were not detected by Alcian blue periodic acid-Schiff staining until Day 4 after LPS treatment and became more abundant in number as well as in mucus content on Day 7. The expression of Muc5ac messenger RNA (mRNA) as well as glycoprotein was enhanced on Day 2, peaked on Day 4, and decreased on Day 7, whereas enhanced expression of mucin core 2 β 6 N-acetylglucosaminyltransferase (C2GnT)-M mRNA was not detected until Day 4 and peaked on Day 7. The expression of C2GnT-L mRNA in the lung, a marker for activated leukocytes as well as mucus cells, peaked on Day 2 and remained moderately high until Day 7. C2GnT-L mRNA expression in LPS-treated lung correlated with the presence of neutrophils and the appearance of mucus cells in the airway epithelium. We conclude that mucus cell metaplasia and hyperplasia can be generated in mouse lungs with a single intratracheal instillation of LPS. In addition, C2GnT-M may serve as a marker for mucus cells in mouse lung. This LPS-induced mucus cell metaplasia and hyperplasia model should be useful for the study ofPseudomonas-induced airway mucus hypersecretory diseases.