Published online before print May 5, 2008

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(American Journal of Pathology. 2008;172:1457-1466.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070593

Review

Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

Livija Deban, Carmen Correale, Stefania Vetrano, Alberto Malesci^* and Silvio Danese^*

From the Division of Gastroenterology,^* and the Laboratory for Immunology and Inflammation, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Clinico Humanitas, Rozzano, Milan; and the University of Milan, Milan, Italy

Abstract

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.