Time course of endothelial cell proliferation and microvascular remodeling in chronic inflammation
Time course of endothelial cell proliferation and microvascular remodeling in chronic inflammation
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DOI：
10.1016/s0002-9440(10)64676-7
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发表时间：
2001-06-01
影响因子：
6
通讯作者：
McDonald, M
中科院分区：
文献类型：
--
作者：
Ezaki, T;Baluk, P;McDonald, M
血管生成和血管重塑是许多慢性炎症性疾病的特征。当疾病缓慢发展时，微血管系统的伴随变化似乎同样是渐进的。在这里，我们报告说，在导致慢性炎症性气道疾病的感染发生后，内皮细胞增殖率和血管尺寸迅速增加。在接种肺支原体的 C3H 小鼠中，通过灌注番茄凝集素使气管微血管系统可见，在感染后 4 至 7 天迅速扩大，然后趋于稳定。小动脉、毛细血管和小静脉的直径分别平均增加 148%、214% 和 74%。通过溴脱氧尿苷 (BrdU) 标记测量内皮细胞增殖，在 5 天时达到峰值（无病原体值的 18 倍），直到第 9 天急剧下降，但在至少 28 天内保持在与无病原体值的 3 倍相似的水平。重塑的毛细血管和小静脉是局灶性血浆渗漏和广泛白细胞粘附的部位。感染的大多数全身表现发生在内皮增殖高峰之后很久，对肺支原体的体液免疫反应是最晚出现的，在14天后增强。这些数据表明，内皮细胞增殖和微血管重塑发生在慢性气道疾病的早期阶段，并表明血管变化先于广泛的组织重塑。
Angiogenesis and vascular remodeling are features of many chronic inflammatory diseases. When diseases evolve slowly, the accompanying changes in the microvasculature would seem to be similarly gradual. Here we report that the rate of endothelial cell proliferation and the size of blood vessels increases rapidly after the onset of an infection that leads to chronic inflammatory airway disease. In C3H mice inoculated with Mycoplasma pulmonis, the tracheal microvasculature, made visible by perfusion of Lycopersicon esculentum lectin, rapidly enlarged from 4 to 7 days after infection and then plateaued, Diameters of arterioles, capillaries, and venules increased on average 148, 214, and 74%, respectively. Endothelial cell proliferation, measured by bromodeoxyuridine (BrdU) labeling, peaked at 5 days (18 times the pathogen-free value), declined sharply until day 9, but remained at similar to3 times the pathogen-free value for at least 28 days. Remodeled capillaries and venules were sites of focal plasma leakage and extensive leukocyte adherence. Most systemic manifestations of the infection occurred well after the peak of endothelial proliferation, and the humoral immune response to M, pulmonis was among the latest, increasing after 14 days. These data show that endothelial cell proliferation and microvascular remodeling occur at an early stage of chronic airway disease and suggest that the vascular changes precede widespread tissue remodeling.