凋亡的中性粒细胞和T细胞在免疫反应消退过程中通过调节CCR5表达来隔离趋化因子。

Ariel Amiram, Fredman Gabrielle, Sun Yee-Ping, Kantarci Alpdogan, Van Dyke Thomas E, Luster Andrew D, Serhan Charles N

Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

Nat Immunol. 2006 Nov;7(11):1209-16. doi: 10.1038/ni1392. Epub 2006 Oct 1.

During the resolution phase of inflammation, the 'corpses' of apoptotic leukocytes are gradually cleared by macrophages. Here we report that during the resolution of peritonitis, the CCR5 chemokine receptor ligands CCL3 and CCL5 persisted in CCR5-deficient mice. CCR5 expression on apoptotic neutrophils and activated apoptotic T cells sequestered and effectively cleared CCL3 and CCL5 from sites of inflammation. CCR5 expression on late apoptotic human polymorphonuclear cells was downregulated by proinflammatory stimuli, including tumor necrosis factor, and was upregulated by 'proresolution' lipid mediators, including lipoxin A4, resolvin E1 and protectin D1. Our results suggest that CCR5+ apoptotic leukocytes act as 'terminators' of chemokine signaling during the resolution of inflammation.

在炎症消退阶段，凋亡白细胞的“尸体”逐渐被巨噬细胞清除。在此我们报告，在腹膜炎消退过程中，CCR5趋化因子受体配体CCL3和CCL5在CCR5缺陷小鼠中持续存在。凋亡中性粒细胞和活化凋亡T细胞上的CCR5表达隔离并有效清除炎症部位的CCL3和CCL5。促炎刺激（包括肿瘤坏死因子）可下调晚期凋亡人多形核细胞上的CCR5表达，而“促消退”脂质介质（包括脂氧素A4、消退素E1和保护素D1）则可上调其表达。我们的结果表明，CCR5+凋亡白细胞在炎症消退过程中充当趋化因子信号的“终结者”。