Barnathan E S, Raghunath P N, Tomaszewski J E, Ganz T, Cines D B
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6060, USA.
Am J Pathol. 1997 Mar;150(3):1009-20.
Neutrophil defensins comprise a family of cationic peptides that possess potent antimicrobial activity. Defensins are normally sequestered in cytoplasmic granules with their primary site of action in phagolysosomes, although some peptide is released into the circulation during the course of infection or inflammation. In view of the fact that neutrophils adhere to the endothelium and that defensins have been reported to bind to human endothelial cells in vitro, we used immunohistochemistry to study the distribution of these peptides in normal and in atherosclerotic human coronary arteries. Defensin was found primarily in the intima of normal and atherosclerotic vessels, most prominently in association with intimal smooth muscle cells. Both large- and small-vessel endothelium stained focally for defensin. Defensin was also found in the media near the external elastic lamina and in some periadventitial vessels. The same distribution was seen in vessels that had been perfusion fixed immediately upon procurement, excluding diffusion of defensin from PMNs ex vivo. These data indicate that neutrophil defensin is present in the walls of human coronary arteries. The deposition of defensin in vessels may contribute to the pathophysiological consequences of inflammation in addition to their role in host defense.
中性粒细胞防御素是一类具有强大抗菌活性的阳离子肽家族。防御素通常被隔离在细胞质颗粒中,其主要作用位点在吞噬溶酶体中,不过在感染或炎症过程中会有一些肽释放到循环系统中。鉴于中性粒细胞会黏附在内皮细胞上,且有报道称防御素在体外可与人内皮细胞结合,我们采用免疫组织化学方法研究了这些肽在正常和动脉粥样硬化的人冠状动脉中的分布情况。发现防御素主要存在于正常血管和动脉粥样硬化血管的内膜中,最显著的是与内膜平滑肌细胞相关。大小血管的内皮细胞均有局灶性防御素染色。在靠近外弹力膜的中膜以及一些外膜周围血管中也发现了防御素。在取材后立即进行灌注固定的血管中也观察到了相同的分布情况,排除了防御素在体外从多形核白细胞扩散的可能性。这些数据表明人冠状动脉壁中存在中性粒细胞防御素。防御素在血管中的沉积除了在宿主防御中发挥作用外,可能还会导致炎症的病理生理后果。