Center for Lung Biology, University of Washington, Seattle, WA, USA.
Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Matrix Biol. 2018 Nov;73:34-51. doi: 10.1016/j.matbio.2018.01.018. Epub 2018 Mar 23.
Several studies have implicated a causative role for specific matrix metalloproteinases (MMPs) in the development and progression of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) and its severe sequela, emphysema. However, the precise function of any given MMP in emphysema remains an unanswered question. Emphysema results from the degradation of alveolar elastin - among other possible mechanisms - a process that is often thought to be caused by elastolytic proteinases made by macrophages. In this article, we discuss the data suggesting, supporting, or refuting causative roles of macrophage-derived MMPs, with a focus on MMPs-7, -9, -10, -12, and 28, in both the human disease and mouse models of emphysema. Findings from experimental models suggest that some MMPs, such as MMP-12, may directly breakdown elastin, whereas others, particularly MMP-10 and MMP-28, promote the development of emphysema by influencing the proteolytic and inflammatory activities of macrophages.
多项研究表明，特定基质金属蛋白酶（MMPs）在香烟烟雾引起的慢性阻塞性肺疾病（COPD）及其严重后果肺气肿的发展和进展中起致病作用。然而，任何特定 MMP 在肺气肿中的精确功能仍然是一个未解决的问题。肺气肿是由肺泡弹性蛋白的降解引起的-除其他可能的机制外-这一过程通常被认为是由巨噬细胞产生的弹性蛋白水解蛋白酶引起的。在本文中，我们讨论了支持、支持或反驳巨噬细胞衍生 MMPs 的因果作用的数据，重点是 MMPs-7、-9、-10、-12 和 28 在人类疾病和肺气肿的小鼠模型中的作用。实验模型的结果表明，一些 MMPs（如 MMP-12）可能直接分解弹性蛋白，而其他 MMPs，特别是 MMP-10 和 MMP-28，通过影响巨噬细胞的蛋白水解和炎症活性来促进肺气肿的发展。
