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自噬调节内皮细胞连接来抑制炎症期间的中性粒细胞渗出
作者:小柯机器人 发布时间:2021/8/9 13:24:23

英国伦敦玛丽女王大学Sussan Nourshargh、Natalia Reglero-Real等研究人员合作发现,自噬调节内皮细胞连接来抑制炎症期间的中性粒细胞渗出。2021年8月6日,《免疫》杂志在线发表了这项成果。

研究人员证明,炎症组织中的静脉内皮细胞(EC)表现出强大的自噬反应,这种反应在时间上与中性粒细胞运输的高峰相一致,并严格定位在EC的接触点上。在小鼠的炎症模型中,遗传性地降低细胞自噬会导致过多的中性粒细胞跨内皮细胞迁移和不受控制的白细胞迁移,而药物诱导自噬会抑制中性粒细胞渗入组织。从机制上讲,自噬调节了EC连接的重塑和关键EC粘附分子的表达,从而促进了它们在细胞内的运输和降解。总的来说,研究人员发现,自噬是EC白细胞运输机器的一种调节因子,可用于终止生理性炎症。

据介绍,中性粒细胞从血液循环中迁移到感染或损伤部位是一个关键的免疫反应,这需要突破排列在血管内部的内皮细胞。不受控制的中性粒细胞跨内皮细胞迁移是致病性的,但其生理终止的分子基础仍然未知。

附:英文原文

Title: Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation

Author: Natalia Reglero-Real, Lorena Pérez-Gutiérrez, Azumi Yoshimura, Loc Rolas, José Garrido-Mesa, Anna Barkaway, Catherine Pickworth, Rebeca S. Saleeb, Maria Gonzalez-Nuez, Shani N. Austin-Williams, Dianne Cooper, Laura Vázquez-Martínez, Tao Fu, Giulia De Rossi, Matthew Golding, Mathieu Benoit-Voisin, Chantal M. Boulanger, Yoshiaki Kubota, William A. Muller, Sharon A. Tooze, Thomas D. Nightingale, Lucy Collinson, Mauro Perretti, Ezra Aksoy, Sussan Nourshargh

Issue&Volume: 2021-08-06

Abstract: The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation.

DOI: 10.1016/j.immuni.2021.07.012

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00298-3

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx