Cigarette smoke triggers macrophage adhesion and activation: Role of lipid peroxidation products and scavenger receptor
Cigarette smoke triggers macrophage adhesion and activation: Role of lipid peroxidation products and scavenger receptor
复制标题
DOI：
10.1016/s0891-5849(03)00390-3
复制
发表时间：
2003-10-01
影响因子：
7.4
通讯作者：
Calvez, R
中科院分区：
文献类型：
--
作者：
Kirkham, PA;Spooner, G;Calvez, R
慢性阻塞性肺疾病（COPD）的肺气肿的特征是肺泡壁的破坏导致远端呼吸空间的永久性扩大。一个主要的致病因素是吸烟，它会在肺部产生慢性氧化应激。在细胞水平上，肺泡间隙内巨噬细胞积聚和滞留的增加对肺气肿的发展至关重要。迄今为止，关于慢性氧化应激与巨噬细胞积累和滞留的潜在机制尚不清楚。我们的研究旨在确定香烟烟雾和脂质过氧化产物对细胞外基质蛋白的修饰对巨噬细胞粘附和活化的作用。与未修饰的胶原相比，香烟烟雾修饰的胶原IV上粘附的巨噬细胞数量增加，未修饰的胶原很少或没有粘附的巨噬细胞。当胶原蛋白被丙烯醛或4-羟基-2-壬烯醛修饰时，也得到了类似的观察结果。粘连可以用岩藻聚糖或针对a型巨噬细胞清道夫受体的单克隆抗体阻断。此外，修饰后的胶原蛋白可触发巨噬细胞的氧化破裂和MCP-1释放。因此，这些结果强调了一种潜在的机制，即氧化应激通过产生活性羰基促进巨噬细胞的积累、保留和激活，而不依赖于其他促炎刺激。本文讨论了这对慢性阻塞性肺病肺气肿发展的影响。(C) 2003 Elsevier Inc.
Pulmonary emphysema in chronic obstructive pulmonary disease (COPD) is characterized by the destruction of the alveolar walls leading to permanent enlargement of distal respiratory air spaces. A major causal factor is cigarette smoking, which produces conditions of chronic oxidative stress within the lungs. At a cellular level, increased macrophage accumulation and retention within the alveolar interstitial spaces is pivotal to the development of emphysema. To date it has been unclear as to the underlying mechanisms relating chronic oxidative stress to macrophage accumulation and retention. Our study was initiated to ascertain the role of modification of extracellular matrix proteins with cigarette smoke and products of lipid peroxidation on macrophage adhesion and activation. Increased numbers of macrophages were seen adhering to cigarette smoke-modified collagen IV as compared to unmodified collagen, where little or no adherent macrophages were observed. Similar observations were made when collagen was modified with either acrolein or 4-hydroxy-2-nonenal. Adhesion could be blocked with either fucoidan or a monoclonal antibody against the Type A macrophage scavenger receptor. Also, modified collagen triggered both oxidative burst and MCP-1 release in macrophages. These results, therefore, highlight a potential mechanism by which oxidative stress through the production of reactive carbonyls promotes macrophage accumulation, retention, and activation, independently of other proinflammatory stimuli. The implications of this for the development of emphysema in COPD are discussed. (C) 2003 Elsevier Inc.