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.

多形核白细胞 （PMN） 在迁移穿过限制性内皮细胞连接时遇到的机械力对多形核白细胞 （PMN） 功能的调节尚不清楚。使用遗传、成像、微流控和 体内方法，我们证明了 PMN 质体中的机械传感器 Piezo1 在跨内皮迁移过程中诱导了刺突样 Ca²⁺ 信号。机械感应增加了 PMN 进入组织的杀菌功能。PMN 中的 Piezo1 基因缺失的小鼠清除细菌有缺陷，它们的肺部易发生严重感染。将 Piezo1 激活的 PMN 过继转移到铜绿假单胞菌感染小鼠的肺部或将 PMN 暴露在微流体系统中的特定机械力下，改善了 PMN 的细菌清除表型。Piezo1 转导了迁移过程中激活的机械信号，以上调烟酰胺腺嘌呤二核苷酸磷酸 （NADPH） 氧化酶 4，这对增加 PMN 杀菌活性至关重要。因此，PMN 张力增加的 Piezo1 机械感应，同时穿过狭窄的内皮粘附连接，是激活迁移 PMN 的宿主防御功能的中枢机制。