Granucci Francesca, Petralia Filippo, Urbano Matteo, Citterio Stefania, Di Tota Francesco, Santambrogio Laura, Ricciardi-Castagnoli Paola
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy.
Blood. 2003 Oct 15;102(8):2940-7. doi: 10.1182/blood-2002-12-3651. Epub 2003 Jul 3.
Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor expressed in peritoneal macrophages and in a subpopulation of macrophages in the marginal zone of the spleen and in the medullary cord of lymph nodes. By global gene expression analysis, it has been found that the MARCO mRNA was one of the most up-regulated in splenic dendritic cells (DCs) following lipopolysaccharide or bacterial activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated microglial cells. Here we show that MARCO is expressed on splenic DCs at late time points after activation and that its expression correlates with profound changes in actin cytoskeleton organization in DCs and microglia. During maturation, DCs undergo profound rearrangements of actin cytoskeleton. Immature DCs are adherent with visible actin cables, while fully mature, MARCO-expressing, splenic DCs are nonadherent, round in shape, and have an actin cytoskeleton with a punctate distribution. The simple expression of MARCO was sufficient to induce these cytoskeleton modifications in DCs. MARCO-transfected immature DCs acquired a typical morphology of mature DCs and did not rearrange the actin cytoskeleton following activation. Moreover, DCs in which MARCO was knocked down did not reach the mature phenotype and maintained the typical morphology of transitional DCs. MARCO expression in DCs and microglial cells was also associated with a decrease of antigen internalization capacity. Thus, the MARCO receptor is important for actin cytoskeleton rearrangements and the down-regulation of antigen uptake function during DC and microglial cell maturation.
具有胶原结构的巨噬细胞受体（MARCO）是一种清道夫受体，在腹膜巨噬细胞、脾脏边缘区的巨噬细胞亚群以及淋巴结髓索中表达。通过全基因组表达分析发现，在脂多糖或细菌激活后，脾树突状细胞（DC）中MARCO mRNA是上调最为显著的基因之一，在粒细胞-巨噬细胞集落刺激因子（GM-CSF）处理的小胶质细胞中也是如此。在此我们表明，MARCO在激活后的晚期在脾DC上表达，并且其表达与DC和小胶质细胞中肌动蛋白细胞骨架组织的深刻变化相关。在成熟过程中，DC经历肌动蛋白细胞骨架的深刻重排。未成熟DC贴壁，有可见的肌动蛋白束，而完全成熟、表达MARCO的脾DC不贴壁，呈圆形，具有点状分布的肌动蛋白细胞骨架。MARCO的简单表达足以在DC中诱导这些细胞骨架修饰。转染了MARCO的未成熟DC获得了成熟DC的典型形态，并且在激活后不会重排肌动蛋白细胞骨架。此外，敲低MARCO的DC未达到成熟表型，维持了过渡性DC的典型形态。DC和小胶质细胞中MARCO的表达也与抗原内化能力的降低相关。因此，MARCO受体对于DC和小胶质细胞成熟过程中的肌动蛋白细胞骨架重排以及抗原摄取功能的下调很重要。
