Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, 130 Dongan Road, Building 7, Room 214, Shanghai, 200032, PR China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, 130 Dongan Road, Building 7, Room 214, Shanghai, 200032, PR China.
Toxicol Lett. 2019 Mar 1;302:60-74. doi: 10.1016/j.toxlet.2018.11.002. Epub 2018 Nov 15.
Fine ambient particle matter (PM2.5) induces inflammatory lung injury; however, whether intratracheal administration of PM2.5 increases pulmonary polymorphonuclear leukocyte (PMN) infiltration, the mechanism of infiltration, and if these cells exacerbate PM2.5-induced lung injury are unknown.
Using 32,704 subjects, the association between blood PMNs and ambient PM2.5 levels on the previous day was retrospectively analyzed. Neutropenia was achieved by injecting mice with PMN-specific antibodies. Inhibition of PMN infiltration was achieved by pretreating PMNs with soluble vascular cell adhesion molecule-1 (sVCAM-1). The effects of PMNs on PM2.5-induced lung injury and endothelial dysfunction were observed.
Short-term PM2.5 (> 75 μg/m air) exposure increased the PMN/white blood cell ratio and the PMN count in human peripheral blood observed during routine examination. A significant number of PM2.5-treated PMNs was able to bind sVCAM-1. In mice, intratracheally-instilled PM2.5 deposited in the alveolar space and endothelial cells, which caused significant lung edema, morphological disorder, increased permeability of the endothelial-alveolar epithelial barrier, and PMN infiltration with increased VCAM-1 expression. Depletion of circulatory PMNs inhibited these adverse effects. Replenishment of untreated PMNs, but not those pretreated with soluble VCAM-1, restored lung injury. In vitro, PM2.5 increased VCAM-1 expression and endothelial and epithelial monolayer permeability, and promoted PMN adhesion to, chemotaxis toward, and migration across these monolayers. PMNs, but not those pretreated with soluble VCAM-1, exacerbated these effects.
VCAM-1-mediated PMN infiltration was essential for a detrimental cycle of PM2.5-induced inflammation and lung injury. Results suggest that drugs that inhibit PMN function might prevent acute deterioration of chronic pulmonary and cardiovascular diseases triggered by PM2.5.
细颗粒物（PM2.5）会引起肺部炎症损伤；然而，气管内给予 PM2.5 是否会增加肺部多形核白细胞（PMN）浸润、浸润的机制，以及这些细胞是否会加剧 PM2.5 引起的肺损伤尚不清楚。
使用 32704 名受试者，回顾性分析了前一天血液 PMN 与环境 PM2.5 水平之间的关系。通过注射 PMN 特异性抗体使中性粒细胞减少。通过用可溶性血管细胞黏附分子-1（sVCAM-1）预处理 PMN 来抑制 PMN 浸润。观察 PMN 对 PM2.5 诱导的肺损伤和内皮功能障碍的影响。
短期 PM2.5（>75μg/m 空气）暴露增加了人类外周血常规检查中观察到的 PMN/白细胞比值和 PMN 计数。大量 PM2.5 处理的 PMN 能够结合 sVCAM-1。在小鼠中，气管内滴注的 PM2.5 沉积在肺泡空间和内皮细胞中，导致明显的肺水肿、形态紊乱、内皮-肺泡上皮屏障通透性增加以及 PMN 浸润和 VCAM-1 表达增加。循环 PMN 的耗竭抑制了这些不良反应。未处理的 PMN 补充，但不是用可溶性 VCAM-1 预处理的 PMN 补充，恢复了肺损伤。体外，PM2.5 增加了 VCAM-1 表达和内皮细胞和上皮细胞单层通透性，并促进了 PMN 对这些单层的黏附和趋化作用以及迁移。PMN，但不是用可溶性 VCAM-1 预处理的 PMN，加剧了这些作用。
VCAM-1 介导的 PMN 浸润是 PM2.5 诱导的炎症和肺损伤的恶性循环的关键因素。结果表明，抑制 PMN 功能的药物可能预防 PM2.5 引发的慢性肺部和心血管疾病的急性恶化。
