McComb Jennifer G, Ranganathan Mrunalini, Liu Xiang Hong, Pilewski Joseph M, Ray Prabir, Watkins Simon C, Choi Augustine M K, Lee Janet S
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Am J Pathol. 2008 Oct;173(4):949-61. doi: 10.2353/ajpath.2008.071034. Epub 2008 Sep 4.
CX3CR1 is expressed on monocytes, dendritic cells, macrophages, subsets of T lymphocytes, and natural killer cells and functions in diverse capacities such as leukocyte adhesion, migration, and cell survival on ligand binding. Expression of the CX3CL1 gene, whose expression product is the sole ligand for CX3CR1, is up-regulated in human lungs with chronic cigarette smoke-induced obstructive lung disease. At present, it is unknown whether CX3CL1 up-regulation is associated with the recruitment and accumulation of immune cells that express CX3CR1. We show that mice chronically exposed to cigarette smoke up-regulate CX3CL1 gene expression, which is associated with an influx of CX3CR1+ cells in the lungs. The increase in CX3CR1+ cells is primarily comprised of macrophages and T lymphocytes and is associated with the development of emphysema. In alveolar macrophages, cigarette smoke exposure increased the expression of both CX3CR1 and CX3CL1 genes. The inducibility of CX3CR1 expression was not solely dependent on a chronic stimulus because lipopolysaccharide up-regulated CX3CR1 in RAW264.7 cells in vitro and in mononuclear phagocytes in vivo. Our findings suggest a mechanism by which macrophages amplify and promote CX3CR1+ cell accumulation within the lungs during both acute and chronic inflammatory stress. We suggest that one function of the CX3CR1-CX3CL1 pathway is to recruit and sustain divergent immune cell populations implicated in the pathogenesis of cigarette smoke-induced emphysema.
CX3CR1在单核细胞、树突状细胞、巨噬细胞、T淋巴细胞亚群和自然杀伤细胞上表达，在配体结合时具有多种功能，如白细胞黏附、迁移和细胞存活。CX3CL1基因的表达产物是CX3CR1的唯一配体，在患有慢性香烟烟雾诱导的阻塞性肺病的人肺中，CX3CL1基因的表达上调。目前，尚不清楚CX3CL1上调是否与表达CX3CR1的免疫细胞的募集和积累有关。我们发现，长期暴露于香烟烟雾的小鼠CX3CL1基因表达上调，这与肺中CX3CR1+细胞的流入有关。CX3CR1+细胞的增加主要由巨噬细胞和T淋巴细胞组成，并与肺气肿的发展有关。在肺泡巨噬细胞中，香烟烟雾暴露增加了CX3CR1和CX3CL1基因的表达。CX3CR1表达的诱导性并不完全依赖于慢性刺激，因为脂多糖在体外RAW264.7细胞和体内单核吞噬细胞中上调了CX3CR1。我们的研究结果提示了一种机制，通过该机制巨噬细胞在急性和慢性炎症应激期间在肺内放大并促进CX3CR1+细胞的积累。我们认为，CX3CR1-CX3CL1途径的一个功能是募集和维持与香烟烟雾诱导的肺气肿发病机制有关的不同免疫细胞群体。
