Brass D M, Savov J D, Gavett S H, Haykal-Coates N, Schwartz D A
Pulmonary and Critical Care Medicine, Duke Univ. Medical Center, Research Dr., Rm. 277 MSRB, DUMC Box 2629, Durham, NC 27710-0001, USA.
Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L755-61. doi: 10.1152/ajplung.00001.2003. Epub 2003 Jun 6.
The endotoxin component of organic dusts causes acute reversible airflow obstruction and airway inflammation. To test the hypothesis that endotoxin alone causes airway remodeling, we have compared the response of two inbred mouse strains to subchronic endotoxin exposure. Physiological and biological parameters were evaluated after 1 day, 5 days, or 8 wk of exposure to endotoxin [lipopolysaccharide (LPS)] in endotoxin-sensitive (C3HeB/FeJ) and endotoxin-resistant (C3H/HeJ) mice. After 5 days or 8 wk of LPS exposure, only C3HeB/FeJ had elevated airway hyperreactivity to inhaled methacholine. Only the C3HeB/FeJ mice had significant inflammation of the lower respiratory tract after 1 day, 5 days, or 8 wk of LPS exposure. Stereological measurements of small, medium, and large airways indicated that an 8-wk exposure to LPS resulted in expansion of the submucosal area only in the C3HeB/FeJ mice. Cell proliferation as measured by bromodeoxyuridine incorporation contributed to the expansion of the submucosa and was only significantly elevated in C3HeB/FeJ mice actively exposed to LPS. C3HeB/FeJ mice had significantly elevated levels of interleukin-1beta protein in whole lung lavage after 1 day and 5 days of LPS exposure and significantly elevated protein levels of total and active transforming growth factor-beta1 in whole lung lavage fluid after 5 days of LPS exposure. Our findings demonstrate that subchronic inhalation of LPS results in the development of persistent airway disease in endotoxin-responsive mice.
有机粉尘中的内毒素成分可导致急性可逆性气流阻塞和气道炎症。为了验证内毒素单独导致气道重塑这一假说，我们比较了两种近交系小鼠品系对亚慢性内毒素暴露的反应。在内毒素敏感（C3HeB/FeJ）和内毒素耐受（C3H/HeJ）小鼠中，在暴露于内毒素[脂多糖（LPS）]1天、5天或8周后评估生理和生物学参数。在暴露于LPS 5天或8周后，只有C3HeB/FeJ对吸入的乙酰甲胆碱气道高反应性升高。在暴露于LPS 1天、5天或8周后，只有C3HeB/FeJ小鼠下呼吸道有明显炎症。对小、中、大气道的体视学测量表明，暴露于LPS 8周仅导致C3HeB/FeJ小鼠黏膜下区域扩大。通过溴脱氧尿苷掺入测量的细胞增殖导致黏膜下层扩大，并且仅在主动暴露于LPS的C3HeB/FeJ小鼠中显著升高。在暴露于LPS 1天和5天后，C3HeB/FeJ小鼠全肺灌洗中的白细胞介素-1β蛋白水平显著升高，在暴露于LPS 5天后，全肺灌洗液中总转化生长因子-β1和活性转化生长因子-β1的蛋白水平显著升高。我们的研究结果表明，亚慢性吸入LPS会导致内毒素反应性小鼠发生持续性气道疾病。
