The mechanisms responsible for the increased loss of pulmonary function following acute lung inflammation in chronic obstructive pulmonary disease remain poorly understood. To investigate this process, our laboratory developed a hamster model that uses a single intratracheal instillation of LPS to superimpose an inflammatory response on lungs treated with intratracheal elastase 1 week earlier. Parameters measured at 2 days after LPS included total leukocyte content and percent neutrophils in BAL fluid (BALF), and BALF levels of both total and peptide-free elastin-specific crosslinks, desmosine and isodesmosine (DID). Airspace enlargement, measured by the mean linear intercept method, and relative interstitial elastic fiber surface area were determined at 1 week after LPS. Compared with animals only treated with elastase, those receiving elastase/LPS showed statistically significant increases in mean linear intercept (156.2 vs. 85.5 μm), BALF leukocytes (187 vs. 37.3 × 10⁴ cells), neutrophils (39% vs. 3.4%), and free DID (182% vs. 97% of controls), which exceeded the sum of the individual effects of the two agents. Despite increased elastin breakdown, the elastase/LPS group had significantly greater elastic fiber surface area than controls (49% vs. 26%) owing to fragmentation and splaying of the fibers. Additional experiments showed that the combination of elastin peptides and LPS significantly enhanced their separate effects on BALF neutrophils and BALF DID in vivo and leukocyte chemotaxis in vitro. The results suggest that structural changes in elastic fibers have proinflammatory activity and may contribute to the decline in pulmonary function related to chronic obstructive pulmonary disease exacerbations.

慢性阻塞性肺疾病在急性肺部炎症后导致肺功能丧失的机制尚不清楚。为了研究这一过程，我们的实验室开发了一种仓鼠模型，该模型使用气管内单次LPS气管滴注，以在1周前用气管内弹性蛋白酶治疗的肺部叠加炎症反应。LPS后2天测量的参数包括总白细胞含量和BAL液（BALF）中的中性粒细胞百分率，以及总和无肽弹性蛋白特异性交联，桥糖胺和异桥糖胺（DID）的BALF水平。在LPS后1周测定通过平均线性截距法测量的空域扩大和相对间隙弹性纤维表面积。与仅使用弹性蛋白酶治疗的动物相比，^4个细胞），嗜中性粒细胞（39％比3.4％）和游离DID（182％比对照组的97％），这超过了两种药物各自作用的总和。尽管弹性蛋白分解增加，但弹性蛋白酶/ LPS组的弹性纤维表面积却比对照组大得多（49％比26％），原因是纤维断裂和张开。另外的实验表明，弹性蛋白肽的结合和LPS显著增强的嗜中性粒细胞BALF他们分开的效果和BALF DID体内和白细胞趋化体外。结果表明，弹性纤维的结构变化具有促炎活性，并且可能导致与慢性阻塞性肺疾病恶化相关的肺功能下降。