Heyder J, Beck-Speier I, Ferron G A, Josten M, Karg E, Kreyling W G, Lenz A-G, Maier K L, Reitmeier P, Ruprecht L, Takenaka S, Wohland T, Ziesenis A, Schulz H
Institute for Inhalation Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg/Munich, Germany.
Inhal Toxicol. 2009 Sep;21(11):920-32. doi: 10.1080/08958370802651994.
Sixteen beagle dogs were housed in four large chambers under minimum restraint. They were exposed for 16 months to clean air and individual baseline data of markers were obtained. For 13 months, eight dogs were further exposed to clean air and eight dogs for 6 h/d to 1-microm MMAD (mass median aerodynamic diameter) acidic sulfate particles carrying 25 micromol H(+) m(-3) into their lungs. To establish functional responses (lung function, cell and tissue integrity, redox balance, and non-specific respiratory defense capacity), each exposed animal served as its own control. To establish structural responses, the eight non-exposed animals served as controls. Acidic particles were produced by nebulization of aqueous sodium hydrogen sulfate at pH 1.5. Only subtle exposure-related changes of lung function and structure were detected. A significant increase in respiratory burst function of alveolar macrophages points to a marginal inflammatory response. This can be explained by the significant production of prostaglandin E(2), activating cyclooxygenase-dependent mechanisms in epithelia and thus inhibiting lung inflammation. The non-specific defense capacity was slightly affected, giving increased tracheal mucus velocity and reduced in vivo dissolution of moderately soluble test particles. Hypertrophy and hyperplasia of bronchial epithelia were not observed, but there was an increase in volume density of bronchial glands and a shift from neutral to acidic staining of epithelial secretory cells in distal airways. The acidic exposure had thus no pathophysiological consequences. It is therefore unlikely that long-term inhalation of acidic particles is associated with a health risk.
16只比格犬被安置在四个大房间中，处于最小程度的限制之下。它们暴露于清洁空气中16个月，并获取了标志物的个体基线数据。在接下来的13个月里，8只狗继续暴露于清洁空气中，另外8只狗每天6小时暴露于肺部吸入质量中位空气动力学直径（MMAD）为1微米、携带25微摩尔氢离子/立方米的酸性硫酸盐颗粒环境中。为了确定功能反应（肺功能、细胞和组织完整性、氧化还原平衡以及非特异性呼吸防御能力），每只暴露的动物都作为自身对照。为了确定结构反应，8只未暴露的动物作为对照。酸性颗粒通过雾化pH值为1.5的硫酸氢钠水溶液产生。仅检测到与暴露相关的轻微肺功能和结构变化。肺泡巨噬细胞呼吸爆发功能显著增加表明存在轻微炎症反应。这可以通过前列腺素E2的大量产生来解释，它激活上皮细胞中环氧化酶依赖性机制，从而抑制肺部炎症。非特异性防御能力受到轻微影响，表现为气管黏液速度增加，中度可溶性测试颗粒的体内溶解减少。未观察到支气管上皮细胞肥大和增生，但支气管腺体的体积密度增加，远端气道上皮分泌细胞的染色从中性变为酸性。因此，酸性暴露没有病理生理后果。所以长期吸入酸性颗粒不太可能与健康风险相关。
