Lung environment determines unique phenotype of alveolar macrophages
Lung environment determines unique phenotype of alveolar macrophages
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DOI：
10.1152/ajplung.90625.2008
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发表时间：
2009-06-01
影响因子：
4.9
通讯作者：
Dow, Steven W.
中科院分区：
文献类型：
--
作者：
Guth, Amanda M.;Janssen, William J.;Dow, Steven W.
Guth AM，Janssen WJ，博西奥CM，克劳奇EC，Henson PM，Dow SW.肺环境决定肺泡巨噬细胞的独特表型。美国生理学杂志肺细胞分子生理学296：L936-L946，2009年。首次发表于2009年3月20日; doi：10.1152/ajplung.90625.2008。肺泡巨噬细胞（AM）是肺中最丰富的抗原呈递细胞，它们在调节肺对吸入病原体和过敏原的免疫应答中起关键作用。然而，与其他身体部位的巨噬细胞相比，AM具有不寻常的表型，在许多方面类似于树突状细胞（DC）的表型。因此，为了更全面地定义AM的独特性质，我们将AM的表型和功能与常驻腹腔灌洗液衍生的巨噬细胞（PLM）的表型和功能进行了比较。我们发现AM和PLM之间存在显著的表型差异，特别是在CD 11 c表达方面，我们还观察到AM比PLM具有更好的抗原呈递能力。因此，我们研究了局部气道环境在AM异常表型产生中的作用。我们进行了细胞转移实验，以比较巨噬细胞分化的气道与腹腔。当骨髓巨噬细胞和腹腔巨噬细胞过继转移到气道时，我们观察到CD 11 c表达显著上调。相反，CD 11 c的表达没有上调后，细胞转移到腹腔，而CD 11b的表达显着增加。在体外培养的骨髓贴壁细胞与表面活性蛋白D（SP-D）或粒细胞/巨噬细胞集落刺激因子（GM-CSF）诱导的CD 11 c的表达显着上调，并在体内GM-CSF浓度显着高于支气管肺泡比腹腔灌洗液。最后，GM-CSF-/-小鼠不能产生CD 11 c（+）AM，但CD 11 c（+）AM存在于SP-D-/-小鼠中。然而，从GM-CSF-/-骨髓巨噬细胞转移到野生型小鼠的气道时，可以上调CD 11 c的表达。这些结果表明，气道环境促进了具有独特DC样特征的巨噬细胞的发育，并且这种不寻常的表型在很大程度上是由局部高浓度的GM-CSF和可能的SP-D决定的。
Guth AM, Janssen WJ, Bosio CM, Crouch EC, Henson PM, Dow SW. Lung environment determines unique phenotype of alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 296: L936-L946, 2009. First published March 20, 2009; doi: 10.1152/ajplung.90625.2008.-Alveolar macrophages (AM) are the most abundant antigen-presenting cells in the lungs, and they play a critical role in regulating pulmonary immune responses to inhaled pathogens and to allergens. However, compared with macrophages in other body sites, AM have an unusual phenotype that, in many respects, resembles the phenotype of dendritic cells (DC). Therefore, to more fully define the unique nature of AM, we compared the phenotype and function of AM with the phenotype and function of resident peritoneal lavage-derived macrophages (PLM). We found striking phenotypic differences between AM and PLM, particularly with regard to CD11c expression, and we also observed that AM had a significantly better antigen-presenting capability than PLM. Therefore, we investigated the role of the local airway environment in generation of the unusual phenotype of AM. We carried out cell transfer experiments to compare macrophage differentiation in the airways with that in the peritoneal cavity. We observed significant upregulation of CD11c expression on bone marrow macrophages and peritoneal macrophages when they were adoptively transferred into the airways. In contrast, CD11c expression was not upregulated after cell transfer into the peritoneal cavity, whereas CD11b expression was significantly increased. In vitro, culture of bone marrow-adherent cells with surfactant protein D (SP-D) or granulocyte/macrophage colony-stimulating factor (GM-CSF) induced significant upregulation of CD11c expression, and in vivo GM-CSF concentrations were significantly higher in bronchoalveolar than in peritoneal lavage fluid. Finally, GM-CSF-/- mice failed to develop CD11c(+) AM, but CD11c(+) AM were present in SP-D-/- mice. However, macrophages from GM-CSF-/- bone marrow could upregulate CD11c expression when transferred to the airways of wild-type mice. These results suggest that the airway environment promotes development of macrophages with unique DC-like characteristics and that this unusual phenotype is determined, to a large degree, by locally high concentrations of GM-CSF and, possibly, SP-D.