Smoking-dependent reprogramming of alveolar macrophage polarization: implication for pathogenesis of chronic obstructive pulmonary disease.
Smoking-dependent reprogramming of alveolar macrophage polarization: implication for pathogenesis of chronic obstructive pulmonary disease.
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DOI：
10.4049/jimmunol.0900473
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发表时间：
2009-08-15
期刊：
影响因子：
--
通讯作者：
Crystal RG
中科院分区：
文献类型：
--
作者：
Shaykhiev R;Krause A;Salit J;Strulovici-Barel Y;Harvey BG;O'Connor TP;Crystal RG
当暴露于特定的微环境中时，巨噬细胞分别获得与炎症和组织重塑相关的M1或m2极化表型。肺泡巨噬细胞（AM）直接与吸烟等环境刺激相互作用，而吸烟是慢性阻塞性肺疾病（COPD）的主要危险因素，COPD是一种以肺部炎症和重塑为特征的疾病。通过对24名健康非吸烟者、34名健康吸烟者和12名COPD吸烟者进行支气管肺泡灌洗获得AM的转录谱分析，以检验吸烟是否会改变AM极化导致疾病相关激活表型的假设。分析显示，健康吸烟者AM表现出独特的极化模式，其特征是大量抑制m1相关的炎症/免疫基因，并诱导与组织重塑和免疫调节相关的各种m2极化程序相关的基因。这种相互变化随着COPD的发展而进展，m1相关基因表达最显著下调（与健康非吸烟者相比p<0.0001，与健康吸烟者相比p<0.002）， TaqMan实时PCR和流式细胞术证实了这一结果。在逐渐下调的m1相关基因中，编码I型趋化因子CXCL9、CXCL10、CXCL11和CCL5的基因。m2相关程序的进行性激活的特征是诱导组织重塑和免疫调节基因，如MMP2、MMP7和ADORA3。主成分分析显示，极化相关基因的差异表达对吸烟和COPD相关的AM表型有重要贡献。总之，这些数据提供了基于转录组的证据，表明AM可能以非炎症方式促进COPD的发病，因为它们在吸烟诱导下向m1失活、部分m2极化的巨噬细胞重编程。
When exposed to specific microenvironment, macrophages acquire either M1- or M2-polarized phenotypes associated with inflammation and tissue remodeling, respectively. Alveolar macrophages (AM) directly interact with environmental stimuli such as cigarette smoke, the major risk factor for chronic obstructive pulmonary disease (COPD), a disease characterized by lung inflammation and remodeling. Transcriptional profiling of AM obtained by bronchoalveolar lavage of 24 healthy nonsmokers, 34 healthy smokers and 12 COPD smokers was performed to test the hypothesis whether smoking alters AM polarization resulting in a disease-relevant activation phenotype. The analysis revealed that AM of healthy smokers exhibited a unique polarization pattern characterized by substantial suppression of M1-related inflammatory/immune genes and induction of genes associated with various M2-polarization programs relevant to tissue remodeling and immunoregulation. Such reciprocal changes progressed with the development of COPD with M1-related gene expression being most dramatically down-regulated (p<0.0001 vs healthy nonsmokers, p<0.002 vs healthy smokers), results confirmed with TaqMan real-time PCR and flow cytometry. Among progressively down-regulated M1-related genes were those encoding type I chemokines CXCL9, CXCL10, CXCL11, and CCL5. Progressive activation of M2-related program was characterized by induction of tissue remodeling and immunoregulatory genes such as MMP2, MMP7 and ADORA3. Principal component analysis revealed that differential expression of polarization-related genes has substantial contribution to global AM phenotypes associated with smoking and COPD. In summary, the data provides transcriptome-based evidence that AM likely contribute to COPD pathogenesis in non-inflammatory manner due to their smoking-induced reprogramming towards M1-deactivated, partially M2-polarized macrophages.
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DOI：
10.1186/cc5055
发表时间：
2006
期刊：
Critical care (London, England)
影响因子：
--
作者：
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影响因子：
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发表时间：
2004-12-01
影响因子：
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