Max Delbrück Center for Molecular Medicine, Berlin, Germany.
J Clin Invest. 2013 Mar;123(3):1343-7. doi: 10.1172/JCI66580. Epub 2013 Feb 8.
The ELR(+)-CXCL chemokines have been described typically as potent chemoattractants and activators of neutrophils during the acute phase of inflammation. Their role in atherosclerosis, a chronic inflammatory vascular disease, has been largely unexplored. Using a mouse model of atherosclerosis, we found that CXCL5 expression was upregulated during disease progression, both locally and systemically, but was not associated with neutrophil infiltration. Unexpectedly, inhibition of CXCL5 was not beneficial but rather induced a significant macrophage foam cell accumulation in murine atherosclerotic plaques. Additionally, we demonstrated that CXCL5 modulated macrophage activation, increased expression of the cholesterol efflux regulatory protein ABCA1, and enhanced cholesterol efflux activity in macrophages. These findings reveal a protective role for CXCL5, in the context of atherosclerosis, centered on the regulation of macrophage foam cell formation.
ELR(+)-CXCL 趋化因子通常被描述为在炎症急性期中强有力的中性粒细胞趋化因子和激活剂。它们在动脉粥样硬化（一种慢性炎症性血管疾病）中的作用在很大程度上尚未被探索。使用动脉粥样硬化的小鼠模型，我们发现 CXCL5 的表达在疾病进展过程中无论是局部还是全身性地上调，但与中性粒细胞浸润无关。出乎意料的是，抑制 CXCL5 不仅没有益处，反而在小鼠动脉粥样硬化斑块中诱导了显著的巨噬细胞泡沫细胞积累。此外，我们证明了 CXCL5 调节巨噬细胞的激活，增加胆固醇外排调节蛋白 ABCA1 的表达，并增强巨噬细胞中的胆固醇外排活性。这些发现揭示了 CXCL5 在动脉粥样硬化背景下的保护作用，其中心在于调节巨噬细胞泡沫细胞的形成。
