Abumiya T, Masuda J, Kawai J, Suzuki T, Ogata J
National Cardiovascular Center Research Institute, Kinki University School of Medicine, Osaka, Japan.
Lab Invest. 1996 Aug;75(2):125-36.
In hypertensive vascular lesions, various pathologic changes are exhibited. To clarify the mechanisms responsible for this diversity of vascular lesions, we immunohistochemically examined hypertensive vascular lesions in stroke-prone spontaneously hypertensive rats with reference to the distribution of macrophage subsets. The brain, kidney, heart, and aorta were dissected from stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats at 8, 12, 16, and 20 weeks of age. Immunohistochemistry was performed with antibodies against the macrophage markers ED1, ED2, and OX42, the MHC class II antigen marker OX6, the T-lymphocyte markers CD4, CD5, and CD8, and other markers, such as alpha-smooth muscle actin, proliferating cell nuclear antigen, and von Willebrand factor. Fibrinoid necrosis was dominant in the brain, and fibrocellular proliferative lesions were dominant in the kidney. Immunohistochemically, the decreased intensity of alpha-smooth muscle actin immunostaining preceded the formation of vascular lesions. Although preexisting ED2-positive perivascular resident macrophages completely disappeared in fibrinoid necrosis, MHC class II-negative and ED1-positive macrophages were scattered around the lesion and showed phagocytosis in the brain, which indicates that macrophages in fibrinoid necrosis had extravasated and acted only as scavengers. In the kidney, there was extensive accumulation of MHC class II-positive and ED1-positive macrophages with T lymphocytes along the affected arteries. These inflammatory cells seemed to be supplied through the perivascular interstitial space, not through the endothelium, and the accumulation of these cells preceded the development of fibrocellular proliferative lesions. In the heart and aorta, macrophage accumulation was either absent or slight, and vascular lesions were rarely observed. These findings suggest that heterogeneity in the time course of macrophage infiltration and in the distribution of macrophage subsets among the vascular trees of various organs seems to be correlated with the diversity of hypertensive vascular lesions. Differences in the routes that supply macrophages and their functions may determine the pathologic changes in the vascular lesions.
在高血压性血管病变中，会呈现出各种病理变化。为了阐明导致这种血管病变多样性的机制，我们参照巨噬细胞亚群的分布，采用免疫组织化学方法对易卒中自发性高血压大鼠的高血压性血管病变进行了研究。在8、12、16和20周龄时，从易卒中自发性高血压大鼠和Wistar - Kyoto大鼠身上摘取脑、肾、心脏和主动脉。使用针对巨噬细胞标志物ED1、ED2和OX42、MHC II类抗原标志物OX6、T淋巴细胞标志物CD4、CD5和CD8以及其他标志物（如α - 平滑肌肌动蛋白、增殖细胞核抗原和血管性血友病因子）的抗体进行免疫组织化学检测。纤维蛋白样坏死在脑中占主导地位，而纤维细胞增生性病变在肾中占主导地位。免疫组织化学结果显示，α - 平滑肌肌动蛋白免疫染色强度的降低先于血管病变的形成。虽然在纤维蛋白样坏死中预先存在的ED2阳性血管周围常驻巨噬细胞完全消失，但MHC II类阴性和ED1阳性巨噬细胞散在于病变周围，并在脑中表现出吞噬作用，这表明纤维蛋白样坏死中的巨噬细胞已渗出且仅作为清道夫发挥作用。在肾中，MHC II类阳性和ED1阳性巨噬细胞与T淋巴细胞沿着受影响的动脉广泛积聚。这些炎性细胞似乎是通过血管周围间隙而非内皮供应的，并且这些细胞的积聚先于纤维细胞增生性病变的发展。在心脏和主动脉中，巨噬细胞积聚要么不存在要么很轻微，并且很少观察到血管病变。这些发现表明，巨噬细胞浸润的时间进程以及巨噬细胞亚群在各个器官血管树中的分布存在异质性，这似乎与高血压性血管病变的多样性相关。巨噬细胞供应途径及其功能的差异可能决定了血管病变中的病理变化。
