Department of Environmental and Occupational Health, College of Public Health, China Medical University, 11001, Shenyang, China.
Toxicol Appl Pharmacol. 2012 Jan 15;258(2):237-47. doi: 10.1016/j.taap.2011.11.003. Epub 2011 Nov 19.
Inhaling concomitants from Asian sand dust (ASD) may result in exacerbation of pneumonia by the pathogen. The exacerbating effect of ASD on pneumonia induced by Klebsiella pneumoniae (KP) was investigated in ICR mice. The organic substances adsorbed onto ASD collected from the atmosphere of Iki-island in Japan were excluded by heat treatment at 360°C for 30min. ICR mice were instilled intratracheally with ASD at doses of 0.05mg or 0.2mg/mouse four times at 2-week intervals (total dose of 0.2mg or 0.8mg/mouse) and were administrated with ASD in the presence or absence of KP at the last intratracheal instillation. Pathologically, ASD caused exacerbation of pneumonia by KP as shown by increased inflammatory cells within the bronchiolar and the alveolar compartments. ASD enhanced the neutrophil number dose dependently as well as the expression of cytokines (IL-1β, IL-6, IL-12, IFN-γ, TNF-α) and chemokines (KC, MCP-1, MIP-1α) related to KP in BALF. In an in vitro study using RAW264.7 cells, combined treatment of ASD and KP increased gene expression of IL-1β, IL-6, IFN-β, KC, MCP-1, and MIP-1α. The same treatment tended to increase the protein level of IL-1β, TNF-α and MCP-1 in a culture medium compared to each treatment alone. The combined treatment tended to increase the gene expression of Toll-like receptor 2 (TLR2), and NALP3, ASC and caspase-1 compared with KP alone. These results suggest that the exacerbation of pneumonia by ASD+KP was due to the enhanced production of pro-inflammatory mediators via activation of TLR2 and NALP3 inflammasome pathways in alveolar macrophages.
吸入来自亚洲沙尘（ASD）的伴随物可能导致病原体引起的肺炎恶化。本研究在 ICR 小鼠中研究了 ASD 对肺炎克雷伯菌（KP）引起的肺炎的恶化作用。将从日本伊伎岛大气中收集的 ASD 中的吸附有机物通过在 360°C 下热处理 30min 排除。ICR 小鼠在 2 周的间隔内四次通过气管内滴注 0.05mg 或 0.2mg/只的 ASD（每只小鼠的总剂量为 0.2mg 或 0.8mg），并在最后一次气管内滴注时在存在或不存在 KP 的情况下给予 ASD。病理学检查显示，ASD 导致 KP 引起的肺炎恶化，表现为细支气管和肺泡隔内炎症细胞增多。ASD 依赖性地增强中性粒细胞数量以及 BALF 中与 KP 相关的细胞因子（IL-1β、IL-6、IL-12、IFN-γ、TNF-α）和趋化因子（KC、MCP-1、MIP-1α）的表达。在使用 RAW264.7 细胞的体外研究中，ASD 和 KP 的联合处理增加了 IL-1β、IL-6、IFN-β、KC、MCP-1 和 MIP-1α 的基因表达。与单独处理相比，相同的处理在培养基中趋于增加 IL-1β、TNF-α 和 MCP-1 的蛋白水平。与单独用 KP 处理相比，联合处理趋于增加 Toll 样受体 2（TLR2）、NALP3、ASC 和 caspase-1 的基因表达。这些结果表明，ASD+KP 引起的肺炎恶化是由于肺泡巨噬细胞中 TLR2 和 NALP3 炎性小体途径的激活导致促炎介质的产生增加所致。
