Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression
Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression
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DOI：
10.1164/ajrccm.163.2.2004039
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发表时间：
2001-02-01
影响因子：
24.7
通讯作者：
Fahy, JV
中科院分区：
文献类型：
--
作者：
Ordoñez, CL;Khashayar, R;Fahy, JV
气道粘液过多是哮喘发病率和死亡率的重要原因，但粘液积聚与杯状细胞大小、数量和功能之间的关系尚不完全清楚。为了解决这些问题，储存在上皮和杯状细胞的大小和数量的粘蛋白进行了形态测定，粘蛋白基因表达的聚合酶链反应和免疫组化测定支气管内活检13例轻度和中度哮喘和12例健康对照组。在诱导痰中测量分泌的粘蛋白。我们发现哮喘患者气道上皮中储存的粘蛋白比正常人高3倍（p < 0.005）。两组杯状细胞大小相似，但哮喘组杯状细胞数量显著高于对照组（93，043 +/-15，824 vs 41，959 +/-9，230/mm 3，p < 0.05）。在轻度哮喘（FEV 1大于或等于80%pred，n = 7）中，储存的粘蛋白水平与中度哮喘（FEV 1 <80%pred，n = 6）一样高，但分泌的粘蛋白水平显著较低（28.4 +/- 6.3 vs 73.5 +/- 47.5 g/ml，p < 0.05）。对于整个哮喘组，分泌的粘蛋白与储存的粘蛋白呈负相关（r（s）=-0.78，p = 0.007）。粘蛋白基因MUC 5AC在正常人和哮喘患者中均为优势表达基因，哮喘患者MUC 5AC蛋白表达增加。我们的结论是，即使是轻度哮喘与杯状细胞增生和气道上皮中储存的粘蛋白增加，而中度哮喘与增加储存的粘蛋白和分泌的粘蛋白。这些结果表明，急性脱颗粒的增生杯状细胞可能是一种机制，哮喘急性加重轻，中度哮喘和慢性脱颗粒的杯状细胞可能有助于慢性气道狭窄中度哮喘。
Excessive airway mucus is an important cause of morbidity and mortality in asthma, but the relationship between accumulation of mucus and goblet cell size, number, and function is incompletely understood. To address these questions, stored mucin in the epithelium and goblet cell size and number were measured morphometrically, and mucin gene expression was measured by polymerase chain reaction and immunohistochemistry in endobronchial biopsies from 13 subjects with mild and moderate asthma and from 12 healthy control subjects. Secreted mucin was measured in induced sputum. We found that stored mucin in the airway epithelium was three times higher than normal in the subjects with asthma (p < 0.005). Goblet cell size was similar in both groups, but goblet cell number was significantly higher in the subjects with asthma (93,043 +/- 15,824 versus 41,959 +/- 9,230/mm(3), p < 0.05). In mild asthma (FEV1 greater than or equal to 80% pred, n = 7), the level of stored mucin was as high as in moderate asthma (FEV1 < 80% pred, n = 6), but the level of secreted mucin was significantly lower (28.4 +/- 6.3 versus 73.5 +/- 47.5 g/ml, p < 0.05). Secreted mucin was inversely correlated with stored mucin for the whole asthma group (r(s) = -0.78, p = 0.007). MUC5AC was the predominant mucin gene expressed in healthy subjects and subjects with asthma, and MUC5AC protein was increased in the subjects with asthma. We conclude that even mild asthma is associated with goblet cell hyperplasia and increased stored mucin in the airway epithelium, whereas moderate asthma is associated with increased stored mucin and secreted mucin. These findings suggest that acute degranulation of hyperplastic goblet cells may represent a mechanism for asthma exacerbations in mild and moderate asthma and that chronic degranulation of goblet cells may contribute to chronic airway narrowing in moderate asthma.