Deban Livija, Correale Carmen, Vetrano Stefania, Malesci Alberto, Danese Silvio
Division of Gastroenterology, Istituto Clinico Humanitas-IRCCS in Gastroenterology, Viale Manzoni, Rozzano, Milan, Italy.
Am J Pathol. 2008 Jun;172(6):1457-66. doi: 10.2353/ajpath.2008.070593. Epub 2008 May 5.
The etiology of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), is still largely unknown. However, it is now clear that the abnormalities underlying pathogenesis of intestinal inflammation are not restricted to those mediated by classic immune cells but also involve nonimmune cells. In particular, advances in vascular biology have outlined a central and multifaceted pathogenic role for the microcirculation in the initiation and perpetuation of IBD. The microcirculation and its endothelial lining play a crucial role in mucosal immune homeostasis through tight regulation of the nature and magnitude of leukocyte migration from the intravascular to the interstitial space. Chronically inflamed IBD microvessels display significant alterations in microvascular physiology and function compared with vessels from healthy and uninvolved IBD intestine. The investigation into human IBD has demonstrated how endothelial activation present in chronically inflamed IBD microvessels results in a functional phenotype that also includes leakiness, chemokine and cytokine expression, procoagulant activity, and angiogenesis. This review contemplates the newly uncovered contribution of intestinal microcirculation to pathogenesis and maintenance of chronic intestinal inflammation. In particular, we assess the multiple roles of the microvascular endothelium in innate immunity, leukocyte recruitment, coagulation and perfusion, and immune-driven angiogenesis in IBD.
克罗恩病和溃疡性结肠炎是炎症性肠病（IBD）的两种主要形式，其病因在很大程度上仍不清楚。然而，现在很清楚的是，肠道炎症发病机制的潜在异常不仅限于经典免疫细胞介导的那些异常，还涉及非免疫细胞。特别是，血管生物学的进展已经勾勒出微循环在IBD的起始和持续过程中所起的核心和多方面的致病作用。微循环及其内皮衬里通过严格调节白细胞从血管内迁移到间质空间的性质和程度，在黏膜免疫稳态中发挥关键作用。与来自健康和未受累的IBD肠道的血管相比，慢性炎症性IBD微血管在微血管生理学和功能方面表现出显著改变。对人类IBD的研究表明，慢性炎症性IBD微血管中存在的内皮激活如何导致一种功能表型，该表型还包括渗漏、趋化因子和细胞因子表达、促凝血活性和血管生成。本综述探讨了肠道微循环对慢性肠道炎症发病机制和维持的新发现的贡献。特别是，我们评估了微血管内皮在IBD的固有免疫、白细胞募集、凝血和灌注以及免疫驱动的血管生成中的多种作用。
