Becker S, Soukup J M, Gilmour M I, Devlin R B
EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27711, USA.
Toxicol Appl Pharmacol. 1996 Dec;141(2):637-48. doi: 10.1006/taap.1996.0330.
A number of epidemiological studies have associated increased cardiopulmonary mortality and hospital admissions with episodes of high particulate air pollution. Inhaled particles, with a mass median aerodynamic diameter <10 microm (PM10) reach the lower respiratory tract where they are phagocytized by alveolar macrophages (AM). Depending on particle composition, exposed AM may produce reactive oxygen species and inflammatory mediators resulting in vascular permeability changes, airway constriction, tissue injury, and inflammation. In the present study human and rat AM were reacted with a range of environmental particles, including oil fly ash (OFA), diesel dust (DD), and ambient air particles (UAP) collected in four urban centers. AM were tested for a chemiluminescence response induced by the particles as well as IL-6 and TNF production. While OFA in a dose range of 1000-10 microg/2-3 x 10(5) AM caused acute cytotoxicity above 100 microg in both human and rat AM (LDH release at 2 hr), DD and UAP were found to be nontoxic in the same dose range. However, after 20 hr of coincubation, UAP concentrations >167 microg/ml were also cytotoxic. Subcytotoxic concentrations of OFA induced a strong immediate chemiluminescence response by AM. A small but significant chemiluminescence response was induced by two out of three UAP tested, while no chemiluminescence was generated in response to DD. The magnitude of particle-induced chemiluminescence was not predictive of a cytokine response by either human or rat AM. TNF and IL-6 production was strongly induced by UAP over a range of noncytotoxic concentrations of particles. OFA induced only small amounts of TNF in a subset of human AM preparations, but not in rat AM. The AM cytokine response to UAP was partly inhibitable by polymyxin B, but not by the iron chelator deferoxamine, indicating that endotoxins but not transitional iron were cytokine-inducing moieties in the tested UAP preparations.
多项流行病学研究表明，心肺死亡率增加及住院率上升与高浓度的颗粒物空气污染事件有关。吸入的颗粒物，质量中位空气动力学直径小于10微米（PM10），可到达下呼吸道，在那里被肺泡巨噬细胞（AM）吞噬。根据颗粒物的成分，暴露的AM可能产生活性氧和炎症介质，导致血管通透性改变、气道收缩、组织损伤和炎症。在本研究中，将人和大鼠的AM与一系列环境颗粒物进行反应，包括油飞灰（OFA）、柴油粉尘（DD）以及在四个城市中心收集的环境空气颗粒物（UAP）。检测AM对颗粒物诱导的化学发光反应以及IL-6和TNF的产生情况。虽然剂量范围为1000 - 10微克/2 - 3×10⁵个AM的OFA在人和大鼠AM中，剂量高于100微克时会引起急性细胞毒性（2小时时LDH释放），但在相同剂量范围内，DD和UAP被发现无毒性。然而，共孵育20小时后，UAP浓度>167微克/毫升时也具有细胞毒性。亚细胞毒性浓度的OFA可诱导AM产生强烈的即时化学发光反应。在测试的三种UAP中，有两种诱导出了微弱但显著的化学发光反应，但DD未诱导出化学发光反应。颗粒物诱导的化学发光强度并不能预测人和大鼠AM的细胞因子反应。在一系列非细胞毒性浓度的颗粒物作用下，UAP强烈诱导TNF和IL-6的产生。OFA仅在一部分人AM制剂中诱导产生少量TNF，但在大鼠AM中未诱导产生。AM对UAP的细胞因子反应部分可被多粘菌素B抑制，但不能被铁螯合剂去铁胺抑制，这表明在所测试的UAP制剂中，内毒素而非过渡性铁是诱导细胞因子产生的部分。
