Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients.
Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients.
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DOI：
10.1186/1465-9921-6-68
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发表时间：
2005-07-08
影响因子：
5.8
通讯作者：
Schaaf, B
中科院分区：
文献类型：
--
作者：
Droemann, D;Goldmann, T;Tiedje, T;Zabel, P;Dalhoff, K;Schaaf, B
香烟烟雾暴露可诱导肺泡巨噬细胞(AM)和肺泡上皮细胞活化，从而产生炎症介质。这是慢性阻塞性肺疾病(COPD)发病机制中的一个重要环节。呼吸道病原体是病情恶化的主要原因，导致反复的损伤和修复周期。病原菌相关分子模式与寄主之间的相互作用是由模式识别受体(PRR)介导的。在本研究中，我们研究了Toll样受体(TLR)-2、TLR4和CD14在人AM上的表达，并与COPD患者、健康吸烟者和非吸烟者的自体单核细胞进行了比较。研究人群包括14名没有急性加重证据的COPD患者，10名健康吸烟者和17名按年龄分层的健康非吸烟者。用流式细胞仪分析人AM表面TLR2、TLR4和CD14分子的表达，并与自体单核细胞进行比较。应用新研制的HOPE固定剂对支气管肺泡灌洗(BAL)细胞进行原位杂交。COPD患者、吸烟者和非吸烟者AM表面TLR2、TLR4和CD14的表达较自体单核细胞减少。与AM相比，我们检测到COPD患者和吸烟者TLR2的表达降低。此外，与吸烟者和COPD患者相比，非吸烟者AM经内毒素刺激后TLR2的mRNA和蛋白表达增加。我们的数据表明，AM的表型和细胞对微生物刺激的反应与吸烟有关，这可能与下呼吸道宿主防御系统的损害有关。
Cigarette smoke exposure including biologically active lipopolysaccharide (LPS) in the particulate phase of cigarette smoke induces activation of alveolar macrophages (AM) and alveolar epithelial cells leading to production of inflammatory mediators. This represents a crucial mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). Respiratory pathogens are a major cause of exacerbations leading to recurrent cycles of injury and repair. The interaction between pathogen-associated molecular patterns and the host is mediated by pattern recognition receptors (PRR's). In the present study we characterized the expression of Toll-like receptor (TLR)- 2, TLR4 and CD14 on human AM compared to autologous monocytes obtained from patients with COPD, healthy smokers and non-smokers. The study population consisted of 14 COPD patients without evidence for acute exacerbation, 10 healthy smokers and 17 healthy non-smokers stratified according to age. The expression of TLR2, TLR4 and CD14 surface molecules on human AM compared to autologous monocytes was assessed ex vivo using FACS analysis. In situ hybridization was performed on bronchoalveolar lavage (BAL) cells by application of the new developed HOPE-fixative. The expression of TLR2, TLR4 and CD14 on AM from COPD patients, smokers and non-smokers was reduced as compared to autologous monocytes. Comparing AM we detected a reduced expression of TLR2 in COPD patients and smokers. In addition TLR2 mRNA and protein expression was increased after LPS stimulation on non-smokers AM in contrast to smokers and COPD patients. Our data suggest a smoke related change in the phenotype of AM's and the cellular response to microbial stimulation which may be associated with impairment of host defenses in the lower respiratory tract.
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影响因子：
6.4
作者：
Echchannaoui, H;Frei, K;Landmann, R
通讯作者：
Landmann, R
DOI：
10.1164/ajrccm.160.supplement_1.11
发表时间：
1999-11-01
影响因子：
24.7
作者：
Mills, PR;Davies, RJ;Devalia, JL
通讯作者：
Devalia, JL
影响因子：
4.4
作者：
Haehnel, V;Schwarzfischer, L;Rehli, M
通讯作者：
Rehli, M
影响因子：
2.8
作者：
Goldmann, T;Wiedorn, KH;Vollmer, E
通讯作者：
Vollmer, E
DOI：
10.1164/ajrccm.150.3.8087340
发表时间：
1994-09-01
影响因子：
24.7
作者：
MCCREA, KA;ENSOR, JE;HASDAY, JD
通讯作者：
HASDAY, JD