Savov Jordan D, Gavett Stephen H, Brass David M, Costa Daniel L, Schwartz David A
Pulmonary and Critical Care Division, Department of Medicine, Duke University Medical Center and Veterans Affairs Medical Center, Durham, North Carolina 27710, USA.
Am J Physiol Lung Cell Mol Physiol. 2002 Nov;283(5):L952-62. doi: 10.1152/ajplung.00420.2001.
We investigated the role of neutrophils in the development of endotoxin-induced airway disease via systemic neutrophil depletion of C3H/HeBFeJ mice and coincident inhalation challenge with lipopolysaccharide (LPS) over a 4-wk period. Mice were made neutropenic with intraperitoneal injections of neutrophil antiserum before and throughout the exposure period. Experimental conditions included LPS-exposed, antiserum-treated; LPS-exposed, control serum-treated; air-exposed, antiserum-treated; and air-exposed, control serum-treated groups. Physiological, biological, and morphological assessments were performed after a 4-wk exposure and again after a 4-wk recovery period. After the 4-wk exposure, LPS-induced inflammation of the lower airways was significantly attenuated in the neutropenic mice, although airway responsiveness (AR) to methacholine (MCh) remained unchanged. After the recovery period, LPS-exposed neutrophil-replete mice had increased AR to MCh when compared with the LPS-exposed neutropenic animals. Morphometric data indicate that the 4-wk exposure to LPS leads to a substantial expansion of the subepithelial area of the medium-sized airways (90-129 microm diameter) in nonneutropenic mice but not neutropenic mice, and this difference persisted even after the recovery period. Expression of bronchial epithelial and subepithelial transforming growth factor-beta1 (TGF-beta1) was diminished in the challenged neutropenic mice compared with the neutrophil-sufficient mice. These studies demonstrate that neutrophils play a critical role in the development of chronic LPS-induced airway disease.
我们通过对C3H/HeBFeJ小鼠进行全身中性粒细胞清除，并在4周内同时进行脂多糖（LPS）吸入激发，研究了中性粒细胞在内毒素诱导的气道疾病发展中的作用。在暴露期之前及整个期间，通过腹腔注射中性粒细胞抗血清使小鼠中性粒细胞减少。实验条件包括LPS暴露、抗血清处理组；LPS暴露、对照血清处理组；空气暴露、抗血清处理组；以及空气暴露、对照血清处理组。在4周暴露后以及4周恢复期后再次进行生理、生物学和形态学评估。4周暴露后，尽管中性粒细胞减少的小鼠对乙酰甲胆碱（MCh）的气道反应性（AR）保持不变，但LPS诱导的下呼吸道炎症在中性粒细胞减少的小鼠中显著减轻。恢复期后，与LPS暴露的中性粒细胞减少的动物相比，LPS暴露的中性粒细胞充足的小鼠对MCh的AR增加。形态计量学数据表明，4周的LPS暴露导致非中性粒细胞减少小鼠中中等大小气道（直径90 - 129微米）的上皮下面积大幅扩大，但中性粒细胞减少小鼠中未出现这种情况，并且即使在恢复期后这种差异仍然存在。与中性粒细胞充足的小鼠相比，受到激发的中性粒细胞减少的小鼠中支气管上皮和上皮下转化生长因子-β1（TGF-β1）的表达减少。这些研究表明，中性粒细胞在慢性LPS诱导的气道疾病发展中起关键作用。
