美国伊利诺伊大学医学院Asrar B. Malik等研究人员合作发现，跨内皮中性粒细胞迁移通过Piezo1机械传感激活杀菌功能。相关论文于2023年12月12日在线发表在《免疫》杂志上。

研究人员利用遗传、成像、微流控和体内方法证明，多形核白细胞（PMN）质膜中的机械传感器Piezo1在跨内皮迁移过程中诱导脉冲样Ca²⁺信号。机械感应增强了进入组织的PMN杀菌功能。PMN中的Piezo1基因被删除的小鼠在清除细菌方面存在缺陷，其肺部易受严重感染。将Piezo1激活的PMN移入受铜绿假单胞菌感染的小鼠肺部，或在微流体系统中将PMN暴露于确定的机械力下，都能改善PMN的细菌清除表型。

Piezo1通过转运过程中激活的机械信号上调烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶4，这对提高PMN的杀菌活性至关重要。因此，在穿越狭窄的内皮粘连接头时，Piezo1对PMN张力增加的机械传感是激活转运PMN中宿主防御功能的核心机制。

据了解，PMN在跨限制性内皮细胞连接处迁移过程中遇到的机械力对其功能的调节作用尚不十分清楚。

附：英文原文

Title: trans-Endothelial neutrophil migration activates bactericidal function via Piezo1 mechanosensing

Author: Amitabha Mukhopadhyay, Yoshikazu Tsukasaki, Wan Ching Chan, Jonathan P. Le, Man Long Kwok, Jian Zhou, Viswanathan Natarajan, Nima Mostafazadeh, Mark Maienschein-Cline, Ian Papautsky, Chinnaswamy Tiruppathi, Zhangli Peng, Jalees Rehman, Balaji Ganesh, Yulia Komarova, Asrar B. Malik

Issue&Volume: 2023-12-12

Abstract: The regulation of polymorphonuclear leukocyte (PMN) function by mechanical forces encountered during their migration across restrictive endothelial cell junctions is not well understood. Using genetic, imaging, microfluidic, and in vivo approaches, we demonstrated that the mechanosensor Piezo1 in PMN plasmalemma induced spike-like Ca2+ signals during trans-endothelial migration. Mechanosensing increased the bactericidal function of PMN entering tissue. Mice in which Piezo1 in PMNs was genetically deleted were defective in clearing bacteria, and their lungs were predisposed to severe infection. Adoptive transfer of Piezo1-activated PMNs into the lungs of Pseudomonas aeruginosa-infected mice or exposing PMNs to defined mechanical forces in microfluidic systems improved bacterial clearance phenotype of PMNs. Piezo1 transduced the mechanical signals activated during transmigration to upregulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4, crucial for the increased PMN bactericidal activity. Thus, Piezo1 mechanosensing of increased PMN tension, while traversing the narrow endothelial adherens junctions, is a central mechanism activating the host-defense function of transmigrating PMNs.

DOI: 10.1016/j.immuni.2023.11.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00489-2