Smoking is associated with shortened airway cilia.
Smoking is associated with shortened airway cilia.
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DOI：
10.1371/journal.pone.0008157
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发表时间：
2009-12-16
期刊：
影响因子：
3.7
通讯作者：
Crystal RG
中科院分区：
文献类型：
--
作者：
Leopold PL;O'Mahony MJ;Lian XJ;Tilley AE;Harvey BG;Crystal RG
虽然纤毛损伤和纤毛节拍频率降低被认为是吸烟者粘液纤毛清除减少的原因，但理论上纤毛长度也会影响粘液纤毛清除。根据纤毛清除模型预测纤毛长度必须超过6-7微米的呼吸道表面流体深度才能在粘液层产生作用力，我们假设正常吸烟者的呼吸道上皮纤毛高度可能比不吸烟者降低。在醛固定、石蜡包埋的支气管镜活检中评估正常非吸烟者和吸烟者的纤毛长度，并通过纤维支气管镜从人的呼吸道上皮刷取风干和水化的样本。在28例支气管镜活检中，健康吸烟者纤毛长度比不吸烟者减少了15%(p<；0.05)。在39个风干的呼吸道上皮细胞样本中，吸烟者的纤毛长度比不吸烟者减少了13%(p<；0.0001)。对27个样本的独立纤毛长度的分析表明，吸烟者的纤毛长度比不吸烟者减少了9%(p<；0.05)。最后，在16个充分保湿的非固定样本中，吸烟者的纤毛长度比不吸烟者减少了7%(p<；0.05)。通过对呼吸道上皮基因表达的全基因组分析，我们确定了6个纤毛相关基因，它们在健康吸烟者中的表达水平显着低于健康非吸烟者。模型预测纤毛长度的减少会减少粘液纤毛的清除，这表明吸烟相关的呼吸道上皮纤毛短小在吸烟引起的肺部疾病的发病机制中起着重要作用。
Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exceed the 6–7 µm airway surface fluid depth to generate force in the mucus layer, we hypothesized that cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers. Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples were brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced by 15% compared to nonsmokers (p<0.05). In 39 air-dried samples of airway epithelial cells, smoker cilia length was reduced by 13% compared to nonsmokers (p<0.0001). Analysis of the length of individual, detached cilia in 27 samples showed that smoker cilia length was reduced by 9% compared to nonsmokers (p<0.05). Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05). Using genome-wide analysis of airway epithelial gene expression we identified 6 cilia-related genes whose expression levels were significantly reduced in healthy smokers compared to healthy nonsmokers. Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia play a significant role in the pathogenesis of smoking-induced lung disease.
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影响因子：
158.5
作者：
AUERBACH, O;HAMMOND, EC;GARFINKEL, L
通讯作者：
GARFINKEL, L
影响因子：
3.8
作者：
Calderón-Garcidueñas, L;Rodríguez-Alcaraz, A;Morgan, KT
通讯作者：
Morgan, KT
DOI：
10.1165/rcmb.2002-0321oc
发表时间：
2003-09-01
影响因子：
6.4
作者：
Hackett, NR;Heguy, A;Crystal, RG
通讯作者：
Crystal, RG
影响因子：
24.3
作者：
Hylkema, M. N.;Sterk, P. J.;Postma, D. S.
通讯作者：
Postma, D. S.
DOI：
10.1080/00039896.1969.10665482
发表时间：
1969-01-01
期刊：
ARCHIVES OF ENVIRONMENTAL HEALTH
影响因子：
--
作者：
ALBERT, RE;LIPPMANN, M;BRISCOE, W
通讯作者：
BRISCOE, W