VCAM-1-mediated neutrophil infiltration exacerbates ambient fine particle-induced lung injury
VCAM-1-mediated neutrophil infiltration exacerbates ambient fine particle-induced lung injury
复制标题
VCAM-1 介导的中性粒细胞浸润会加剧环境细颗粒引起的肺损伤。
DOI：
10.1016/j.toxlet.2018.11.002
复制
发表时间：
2019-03-01
影响因子：
3.5
通讯作者：
Chen, Sifeng
中科院分区：
文献类型：
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作者：
Cui, Anfeng;Xiang, Meng;Chen, Sifeng
工作背景：环境细颗粒物PM2.5诱导炎性肺损伤;然而，肺内施用PM2.5是否增加肺多形核白细胞（PMN）浸润、浸润的机制以及这些细胞是否加重PM2.5诱导的肺损伤尚不清楚。使用32，704名受试者，回顾性分析了前一天血液PMNs与环境PM2.5水平之间的关联。通过给小鼠注射PMN特异性抗体来实现中性粒细胞减少。用可溶性血管细胞粘附分子-1（sVCAM-1）预处理PMN，可抑制PMN浸润。结果：短期PM2.5（> 75 μ g/m3空气）暴露可使人外周血中性粒细胞/白色血细胞比值和外周血中性粒细胞计数增加;大量PM2.5处理的PMN能够结合sVCAM-1。在小鼠中，肺内灌注的PM2.5沉积在肺泡腔和内皮细胞中，这导致显著的肺水肿、形态学紊乱、内皮-肺泡上皮屏障通透性增加和PMN浸润以及VCAM-1表达增加。消耗循环中性粒细胞抑制这些不良反应。补充未处理的中性粒细胞，而不是那些预先与可溶性VCAM-1，恢复肺损伤。在体外，PM2.5增加VCAM-1的表达和内皮细胞和上皮细胞单层的通透性，并促进PMN粘附，趋化性，并跨越这些单层迁移。结论：VCAM-1介导的PMN浸润对PM2.5诱导的炎症和肺损伤的有害循环是必不可少的。结果表明，抑制PMN功能的药物可能会防止由PM2.5引发的慢性肺和心血管疾病的急性恶化。
Background: 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.Methods: 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.Result: Short-term PM2.5 (> 75 mu g/m(3) 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.Conclusion: 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.