英国伦敦玛丽女王大学Sussan Nourshargh课题组取得最新进展。他们发现，与衰老相关的炎症组织局部环境变化导致嗜中性粒细胞异常运输和随后的远端器官损伤。这一研究成果于2021年5月24日发表在国际顶尖学术期刊《免疫》上。

他们研究了衰老对中性粒细胞渗出的影响。使用共聚焦活体显微镜，他们发现在衰老小鼠中，中性粒细胞粘附于炎症组织中的血管内皮，但表现出较高的逆向内皮迁移（rTEM）频率。嗜中性粒细胞对内皮的逆行破坏是由来自于内皮细胞（EC）交界处的肥大细胞趋化因子CXCL1产生的增加所决定的。非典型趋化因子受体1（ACKR1）的EC表达增加支持了衰老小静脉中的这种促炎性环境。CXCL1的积累导致嗜中性粒细胞趋化因子受体CXCR2脱敏，并导致EC接头内嗜中性粒细胞定向运动性丧失。

荧光追踪显示，在衰老小鼠中，接受rTEM的中性粒细胞重新进入循环并扩散到肺部，引起血管渗漏。因此，源自局部炎症部位的中性粒细胞导致远端器官损伤，暗示与衰老相关的全身炎症失调。

附：英文原文

Title: Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage

Author: Anna Barkaway, Loc Rolas, Régis Joulia, Jennifer Bodkin, Tchern Lenn, Charlotte Owen-Woods, Natalia Reglero-Real, Monja Stein, Laura Vázquez-Martínez, Tamara Girbl, Robin N. Poston, Matthew Golding, Rebecca S. Saleeb, Aude Thiriot, Ulrich H. von Andrian, Johan Duchene, Mathieu-Benoit Voisin, Cleo L. Bishop, David Voehringer, Axel Roers, Antal Rot, Tim Lmmermann, Sussan Nourshargh

Issue&Volume: 2021-05-24

Abstract: Aging is associated with dysregulated immune functions. Here, we investigated the impact of age on neutrophil diapedesis. Using confocal intravital microscopy, we found that in aged mice, neutrophils adhered to vascular endothelium in inflamed tissues but exhibited a high frequency of reverse transendothelial migration (rTEM). This retrograde breaching of the endothelium by neutrophils was governed by enhanced production of the chemokine CXCL1 from mast cells that localized at endothelial cell (EC) junctions. Increased EC expression of the atypical chemokine receptor 1 (ACKR1) supported this pro-inflammatory milieu in aged venules. Accumulation of CXCL1 caused desensitization of the chemokine receptor CXCR2 on neutrophils and loss of neutrophil directional motility within EC junctions. Fluorescent tracking revealed that in aged mice, neutrophils undergoing rTEM re-entered the circulation and disseminated to the lungs where they caused vascular leakage. Thus, neutrophils stemming from a local inflammatory site contribute to remote organ damage, with implication to the dysregulated systemic inflammation associated with aging.

DOI: 10.1016/j.immuni.2021.04.025

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00187-4