Fine particulate matter (PM2.5) is one of the most important components of environmental pollutants and is associated with lung injury. Pyroptosis, a form of programmed cell death mainly mediated by the NLRP3 inflammasome, has been reported to be involved in sepsis-induced or ischemia/reperfusion-induced lung injury. However, the specific mechanisms of pyroptosis in PM2.5-induced lung injury are not yet clear. We constructed macrophage-specific NLRP3 knockout mice to explore the mechanism of PM2.5-induced lung injury in terms of inflammatory response, oxidative stress, and apoptosis levels, including the relationship between these effects and pyroptosis. The results disclosed that PM2.5 exposure increased the infiltration of macrophages and leukocytes and the secretion of inflammatory cytokines, including TNF-α and IL-6, in lung tissue. The activity of antioxidant enzymes, including SOD, GSH-PX, and CAT, significantly decreased, while MDA, the end product of lipid oxidation, remarkably increased. The level of apoptosis in lung tissue, measured by the TUNEL assay and apoptosis-related proteins (BAX and BCL-2), was significantly increased. Macrophage-specific NLRP3 knockout could offset these effects. We further observed that PM2.5 treatment activated the NLRP3 inflammasome and subsequently induced pyroptosis, as evidenced by the increased production of IL-1β and IL-18 and the increase of the protein levels of NLRP3, ASC, caspase-1, and GSDMD, which were inhibited when NLRP3 was knocked out in macrophages. Taken together, these results revealed that NLRP3-mediated macrophage pyroptosis promoted PM2.5-induced lung injury through aggravating inflammation, oxidative stress, and apoptosis. Targeting the inhibition of NLRP3-mediated macrophage pyroptosis provides a new way to study lung injury induced by the exposure to PM2.5.

细颗粒物（PM2.5）是环境污染物中最重要的成分之一，与肺损伤有关。Pyroptosis 是一种主要由 NLRP3 炎性体介导的程序性细胞死亡形式，据报道与败血症诱导或缺血/再灌注诱导的肺损伤有关。然而，PM2.5 引起的肺损伤中细胞焦亡的具体机制尚不清楚。我们构建了巨噬细胞特异性 NLRP3 基因敲除小鼠，从炎症反应、氧化应激和细胞凋亡水平方面探讨 PM2.5 诱导肺损伤的机制，包括这些影响与细胞焦亡之间的关系。结果表明，PM2.5 暴露增加了巨噬细胞和白细胞的浸润以及肺组织中炎性细胞因子（包括 TNF-α 和 IL-6）的分泌。SOD、GSH-PX、CAT等抗氧化酶活性显着降低，而脂质氧化终产物MDA则显着升高。通过 TUNEL 测定和细胞凋亡相关蛋白（BAX 和 BCL-2）测量的肺组织细胞凋亡水平显着增加。巨噬细胞特异性 NLRP3 敲除可以抵消这些影响。我们进一步观察到 PM2.5 处理激活了 NLRP3 炎症小体并随后诱导细胞焦亡，这可以通过增加 IL-1β 和 IL-18 的产生以及 NLRP3、ASC、caspase-1 和 GSDMD 的蛋白质水平增加来证明，当 NLRP3 在巨噬细胞中被敲除时，它们被抑制。总之，这些结果表明 NLRP3 介导的巨噬细胞焦亡通过加重炎症、氧化应激、和细胞凋亡。靶向抑制 NLRP3 介导的巨噬细胞焦亡为研究暴露于 PM2.5 引起的肺损伤提供了一种新方法。