Department of Environmental Science and Engineering, School of Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
J Toxicol Environ Health A. 2010;73(1):41-57. doi: 10.1080/15287390903248901.
Epidemiologic and occupational studies demonstrated that ambient particulate matter (PM) and diesel exhaust particles (DEP) exert deleterious effects on human cardiopulmonary health, including exacerbation of pre-existing lung disease and development of respiratory infections. The effects of ambient PM on lung cell responsiveness are poorly defined. Human alveolar macrophages (AM) were exposed to SRM 1649 (Washington, DC, urban dust; UD), SRM 2975 (forklift diesel exhaust particles; DEP), and fine or coarse ambient PM collected in Chapel Hill, NC, during the late fall (November) and early summer (June) of 2001-2002. AM were subsequently incubated with lipopolysaccharide (LPS), phorbol myristate acetate (PMA), or calcium ionophore A23817 for 6 or 24 h after PM exposure. UD and DEP markedly suppressed O2- release 24 h post-PM exposure. UD exposure significantly inhibited tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 release after exposure to 10 nanog/ml LPS. DEP significantly suppressed only TNF-alpha and IL-6 release. Suppressed cytokine release may also be produced by reduced cellular cytokine production. Data suggested that decreased cytokine release is not produced by the presence of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon. Comparison of TNF-alpha release after LPS, PMA, or A23817 revealed that suppressive effects of UD are LPS dependent, whereas inhibitory effects of DEP may work across multiple mechanistic pathways. November and June Chapel Hill PM exposure stimulated TNF-alpha and IL-8 release before LPS exposure. Fine and coarse November PM exposure markedly suppressed TNF-alpha release 6 h after LPS stimulation, but appeared to exert a stimulatory effect on IL-8 release 24 h after LPS exposure. June fine and coarse PM suppressed IL-8 release after LPS exposure. Data suggest that seasonal influences on PM composition affect AM inflammatory response before and after bacterial exposure. Overall, delayed or inhibited AM immune responses to LPS after PM exposure suggest human exposure to ambient PM may enhance pulmonary susceptibility to respiratory infections.
流行病学和职业研究表明，环境颗粒物（PM）和柴油废气颗粒（DEP）对人体心肺健康有不良影响，包括加重现有肺部疾病和引发呼吸道感染。环境 PM 对肺细胞反应性的影响还没有明确的定义。人类肺泡巨噬细胞（AM）暴露于 2001-2002 年秋季（11 月）和初夏（6 月）在北卡罗来纳州教堂山采集的细颗粒物或粗颗粒物、SRM1649（华盛顿特区城市尘埃；UD）和 SRM2975（叉车柴油机废气颗粒；DEP）中。暴露于 PM 后，AM 随后用脂多糖（LPS）、佛波醇 12-肉豆蔻酸酯 13-乙酸盐（PMA）或钙离子载体 A23817 孵育 6 或 24 小时。暴露于 PM 后 24 小时，UD 和 DEP 明显抑制 O2-释放。UD 暴露显著抑制 10 纳克/毫升 LPS 暴露后的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6 和 IL-8 释放。DEP 仅显著抑制 TNF-α和 IL-6 释放。细胞因子释放减少也可能是由于细胞因子产生减少所致。数据表明，减少细胞因子释放不是由于多环芳烃苯并[a]芘（BaP）的存在所致。比较 LPS、PMA 或 A23817 后 TNF-α的释放表明，UD 的抑制作用依赖于 LPS，而 DEP 的抑制作用可能通过多种机制途径发挥作用。11 月和 6 月教堂山 PM 暴露在 LPS 暴露前刺激 TNF-α和 IL-8 释放。11 月细颗粒物和粗颗粒物暴露明显抑制 LPS 刺激后 6 小时 TNF-α释放，但似乎对 LPS 暴露后 24 小时 IL-8 释放有刺激作用。6 月细颗粒物和粗颗粒物抑制 LPS 暴露后 IL-8 释放。数据表明，PM 成分的季节性影响会影响 AM 在细菌暴露前后的炎症反应。总的来说，暴露于 PM 后 AM 对 LPS 的免疫反应延迟或抑制表明，人类暴露于环境 PM 可能会增加对呼吸道感染的肺部易感性。
