Guth Amanda M, Janssen William J, Bosio Catharine M, Crouch Erika C, Henson Peter M, Dow Steven W
Departments of Clinical Sciences, Colorado State University, Ft. Collins, USA.
Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L936-46. doi: 10.1152/ajplung.90625.2008. Epub 2009 Mar 20.
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.
肺泡巨噬细胞（AM）是肺中最丰富的抗原呈递细胞，它们在调节肺部对吸入病原体和过敏原的免疫反应中起关键作用。然而，与身体其他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的表型和功能与驻留腹膜灌洗来源的巨噬细胞（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CD11c表达方面，并且我们还观察到AM具有比PLM明显更好的抗原呈递能力。因此，我们研究了局部气道环境在AM不寻常表型产生中的作用。我们进行了细胞转移实验，以比较气道中巨噬细胞的分化与腹腔中的分化。我们观察到，当骨髓巨噬细胞和腹膜巨噬细胞被过继转移到气道中时，它们表面的CD11c表达显著上调。相反，细胞转移到腹腔后，CD11c表达未上调，而CD11b表达显著增加。在体外，用表面活性蛋白D（SP-D）或粒细胞/巨噬细胞集落刺激因子（GM-CSF）培养骨髓贴壁细胞可诱导CD11c表达显著上调，并且在体内，支气管肺泡灌洗液中的GM-CSF浓度显著高于腹膜灌洗液。最后，GM-CSF基因敲除（GM-CSF(-/-)）小鼠未能发育出CD11c(+) AM，但SP-D基因敲除（SP-D(-/-)）小鼠中存在CD11c(+) AM。然而，来自GM-CSF(-/-)骨髓的巨噬细胞转移到野生型小鼠气道后能够上调CD11c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由局部高浓度的GM-CSF以及可能的SP-D所决定。
