Koch A E, Kunkel S L, Pearce W H, Shah M R, Parikh D, Evanoff H L, Haines G K, Burdick M D, Strieter R M
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Am J Pathol. 1993 May;142(5):1423-31.
Inflammatory leukocytes play a central role in the pathogenesis of human atherosclerotic disease, from early atherogenesis to the late stages of atherosclerosis, such as aneurysm formation. We have shown previously that human abdominal aortic aneurysms are characterized by the presence of numerous chronic inflammatory cells throughout the vessel wall (Am J Pathol 1990, 137: 1199-1213). The signals that attract lymphocytes and monocytes into the aortic wall in aneurysmal disease remain to be precisely defined. We have studied the production of the chemotactic cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by aortic tissues obtained from 47 subjects. We compared the antigenic production of these cytokines by explants of: 1) human abdominal aneurysmal tissue, 2) occlusive (atherosclerotic) aortas, and 3) normal aortas. IL-8, which is chemotactic for neutrophils, lymphocytes, and endothelial cells was liberated in greater quantities by abdominal aortic aneurysms than by occlusive or normal aortas. Using immunohistochemistry, macrophages, and to a lesser degree endothelial cells, were found to be positive for the expression of antigenic IL-8. Similarly, MCP-1, a potent chemotactic cytokine for monocytes/macrophages, was released by explants from abdominal aortic aneurysms in greater quantities than by explants from occlusive or normal aortas. Using immunohistochemistry, the predominant MCP-1 antigen-positive cells were macrophages and to a lesser extent smooth muscle cells. Our results indicate that human abdominal aortic aneurysms produce IL-8 and MCP-1, both of which may serve to recruit additional inflammatory cells into the abdominal aortic wall, hence perpetuating the inflammatory reaction that may result in the pathology of vessel wall destruction and aortic aneurysm formation.
从动脉粥样硬化的早期发生到晚期阶段，如动脉瘤形成，炎性白细胞在人类动脉粥样硬化疾病的发病机制中起着核心作用。我们之前已经表明，人类腹主动脉瘤的特征是整个血管壁存在大量慢性炎症细胞（《美国病理学杂志》1990年，137卷：1199 - 1213页）。在动脉瘤疾病中，吸引淋巴细胞和单核细胞进入主动脉壁的信号仍有待精确界定。我们研究了从47名受试者获取的主动脉组织中趋化细胞因子白细胞介素 - 8（IL - 8）和单核细胞趋化蛋白 - 1（MCP - 1）的产生情况。我们比较了这些细胞因子在外植体中的抗原产生情况，这些外植体分别来自：1）人类腹主动脉瘤组织，2）闭塞性（动脉粥样硬化性）主动脉，以及3）正常主动脉。对中性粒细胞、淋巴细胞和内皮细胞具有趋化作用的IL - 8，腹主动脉瘤释放的量比闭塞性或正常主动脉更多。通过免疫组织化学发现，巨噬细胞以及程度较轻的内皮细胞，对抗原性IL - 8的表达呈阳性。同样，MCP - 1是一种对单核细胞/巨噬细胞有强大趋化作用的细胞因子，腹主动脉瘤外植体释放的量比闭塞性或正常主动脉外植体更多。通过免疫组织化学，主要的MCP - 1抗原阳性细胞是巨噬细胞，平滑肌细胞的阳性程度较轻。我们的结果表明，人类腹主动脉瘤产生IL - 8和MCP - 1，这两者都可能有助于将更多炎症细胞招募到腹主动脉壁，从而使可能导致血管壁破坏和主动脉瘤形成的病理过程的炎症反应持续存在。
