Zhou Hongwei, Kobzik Lester
Department of Environmental Health, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, 665 Huntington Ave, BLDG 2, Rm. 221, Boston, MA 02115, USA.
Am J Respir Cell Mol Biol. 2007 Apr;36(4):460-5. doi: 10.1165/rcmb.2006-0293OC. Epub 2006 Nov 1.
Particulate air pollution is linked to increased pneumonia epidemiologically and diminished lung bacterial clearance experimentally. We investigated the effect of concentrated ambient particles (CAPs, </= PM(2.5)) on the interaction of murine primary alveolar macrophages (AMs) and the murine macrophage cell line, J774 A.1, with Streptococcus pneumoniae. We found that CAPs increased binding of bacteria by both primary AMs and J774 cells (66.7 +/- 10.6% and 58.9 +/- 4.0%, respectively, n = 4). In contrast to bacterial binding, CAPs decreased internalization in both AMs and J774 (55.4 +/- 8.5% and 54.7 +/- 5.1%, respectively, n = 4). The rate of killing of internalized bacteria was similar, but CAPs caused a decrease in the absolute number of bacteria killed by macrophages, mainly due to decreased internalization. Additional analyses showed that soluble components of CAPs mediated the enhanced binding and decreased internalization of S. pneumoniae. Chelation of iron in soluble CAPs substantially reversed, while addition of iron as ferric ammonium citrate restored inhibition of phagocytosis of S. pneumoniae in vitro. The results identify phagocytic internalization as a specific target for toxic effects of air pollution particles on AMs.
流行病学研究表明，空气中的颗粒物污染与肺炎发病率增加有关，实验研究则显示其会降低肺部细菌清除能力。我们研究了浓缩环境颗粒物（CAPs，≤ PM(2.5)）对小鼠原代肺泡巨噬细胞（AMs）以及小鼠巨噬细胞系J774 A.1与肺炎链球菌相互作用的影响。我们发现，CAPs增加了原代AMs和J774细胞对细菌 的结合（分别为66.7±10.6%和58.9±4.0%，n = 4）。与细菌结合情况相反，CAPs降低了AMs和J774细胞对细菌的内化作用（分别为55.4±8.5%和54.7±5.1%，n = 4）。内化细菌的杀灭率相似，但CAPs导致巨噬细胞杀灭的细菌绝对数量减少，主要原因是内化作用降低。进一步分析表明，CAPs的可溶性成分介导了肺炎链球菌结合增强和内化作用降低。可溶性CAPs中的铁螯合作用可显著逆转这种情况，而添加柠檬酸铁铵形式的铁则可恢复体外对肺炎链球菌吞噬作用的抑制。这些结果表明，吞噬内化作用是空气污染颗粒对AMs产生毒性作用的一个特定靶点。
