CX3CR1+ lung mononuclear phagocytes spatially confined to the interstitium produce TNF-α and IL-6 and promote cigarette smoke-induced emphysema.
CX3CR1+ lung mononuclear phagocytes spatially confined to the interstitium produce TNF-α and IL-6 and promote cigarette smoke-induced emphysema.
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DOI：
10.4049/jimmunol.1003221
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发表时间：
2011-03-01
期刊：
影响因子：
--
通讯作者：
Lee JS
中科院分区：
文献类型：
--
作者：
Xiong Z;Leme AS;Ray P;Shapiro SD;Lee JS
吸烟者和患有慢性阻塞性肺病的人的肺部巨噬细胞数量增加。实验证据表明巨噬细胞在 TNF-a 等炎症介质的形成以及香烟烟雾诱发的肺气肿的进展中发挥着核心作用。我们研究了 CX3CR1 在香烟烟雾暴露后肺部单核吞噬细胞募集、炎症细胞因子反应和组织破坏中的作用。使用在 cx3cr1 基因位点表达 egfp 的小鼠，我们发现肺泡巨噬细胞增加了跨膜配体 CX3CL1 的表达，并且在空腔中可检测到可溶性 CX3CL1，但 cx3cr1GFP/GFP 和 cx3cr1GFP/+ 小鼠未能显示出香烟烟雾将 CX3CR1+ 细胞募集到空腔中。相反，香烟烟雾增加了 CX3CR1+CD11b+ 单核吞噬细胞的积累，这些细胞在空间上局限于肺间质，并且在 CD11c、MHC II 类和自发荧光特性的表达上存在异质性。尽管完整的 CX3CL1–CX3CR1 通路放大了肺部 CX3CR1+CD11b+ 单核吞噬细胞的百分比，但这对于招募并不是必需的。相反，功能性 CX3CR1 是组织结合单核吞噬细胞子集在响应香烟烟雾时产生 TNF-α 和 IL-6 所必需的，而功能性 CX3CR1 的缺失可以保护小鼠免受组织破坏性肺气肿的影响。因此，CX3CR1+“组织驻留”单核吞噬细胞通过产生 TNF-α 和 IL-6 启动对香烟烟雾的先天免疫反应，并能够促进肺气肿。
Increased numbers of macrophages are found in the lungs of smokers and those with chronic obstructive pulmonary disease. Experimental evidence shows the central role of macrophages in elaboration of inflammatory mediators such as TNF-a and the progression toward cigarette smoke-induced emphysema. We investigated the role of CX3CR1 in recruitment of mononuclear phagocytes, inflammatory cytokine responses, and tissue destruction in the lungs after cigarette smoke exposure. Using mice in which egfp is expressed at the locus of the cx3cr1 gene, we show that alveolar macrophages increased transmembrane ligand CX3CL1 expression and soluble CX3CL1 was detectable in the airspaces, but cx3cr1GFP/GFP and cx3cr1GFP/+ mice failed to show recruitment of CX3CR1+ cells into the airspaces with cigarette smoke. In contrast, cigarette smoke increased the accumulation of CX3CR1+CD11b+ mononuclear phagocytes that were spatially confined to the lung interstitium and heterogenous in their expression of CD11c, MHC class II, and autofluorescent property. Although an intact CX3CL1–CX3CR1 pathway amplified the percentage of CX3CR1+CD11b+ mononuclear phagocytes in the lungs, it was not essential for recruitment. Rather, functional CX3CR1 was required for a subset of tissue-bound mononuclear phagocytes to produce TNF-α and IL-6 in response to cigarette smoke, and the absence of functional CX3CR1 protected mice from developing tissue-destructive emphysema. Thus, CX3CR1+ “tissue resident” mononuclear phagocytes initiate an innate immune response to cigarette smoke by producing TNF-α and IL-6 and are capable of promoting emphysema.
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DOI：
10.1073/pnas.95.18.10896
发表时间：
1998-09-01
影响因子：
11.1
作者：
Harrison, JK;Jiang, Y;Feng, LL
通讯作者：
Feng, LL
影响因子：
7
作者：
Dean, Richard A.;Overall, Christopher M.
通讯作者：
Overall, Christopher M.
TLR4/MyD88 诱导的 CD11b+Gr-1 int F4/80+ 非迁移性骨髓细胞抑制肺部的 Th2 效应器功能。
影响因子：
8
作者：
Arora, M.;Poe, S. L.;Oriss, T. B.;Krishnamoorthy, N.;Yarlagadda, M.;Wenzel, S. E.;Billiar, T. R.;Ray, A.;Ray, P.
通讯作者：
Ray, P.
影响因子：
15.9
作者：
Houghton, AM;Quintero, PA;Shapiro, SD
通讯作者：
Shapiro, SD
影响因子：
64.8
作者：
GEARING, AJH;BECKETT, P;WOOLLEY, K
通讯作者：
WOOLLEY, K