Obliterative arteritis with nitric oxide synthase and HLA-DR expression inCrohn's colitis

Background/Aims: To cast light on whether inflammatory vascular injury is a possible pathogenic mechanism in Crohn's disease, the histological charact eristics of vascular lesions were investigated. Methodology: Affected vessels in surgically resected colons from 23 patient s with Crohn's disease, 20 with ulcerative colitis, 7 with ischemic colitis , and 9 normal controls were analyzed by Victoria blue and hematoxylin and eosin staining as well as immunohistochemistry for HLA-DR, nitric oxide syn thase, vascular endothelial growth factor and E-cadherin. Results: Inflammatory-cell infiltrates affecting arteries, accompanied by o bliterative intimal thickening, were more frequent in Crohn's disease cases than in the other groups (P <0.05-0.0001). Crohn's disease activity was po sitively correlated with the degree of obliterative arteritis. Granulomatou s vasculitis was found exclusively in Crohn's disease (10 cases; 43.5%). In addition, focally enhanced endothelial staining of HLA-DR, with expression in granulo-mas adjacent to vessels was occasionally observed. In the endot helium of affected vessels, strong expression of HLA-DR was more prevalent in Crohn's disease and/or ulcerative colitis as compared with the ischemic colitis acid controls (P <0.05-0.01). In the involved arteries, enhanced en dothelial nitric oxide synthase expression was most common in Crohn's disea se among the groups (P <0.05). A few cases of Crohn's disease, ulcerative c olitis and ischemic colitis were positive for inducible nitric oxide syntha se, vascular endothelial growth factor or E-cadherin in the vessel walls. Conclusions: The presence of characteristic obliterative arteritis and gran ulomatous vasculitis, a possible cause of ischemic injury, supports, in par t, a vascular hypothesis for the pathogenesis of Crohn's disease. Enhanced expression of endothelial nitric oxide synthase and HLA-DR possibly reflect s compensatory endothelium-mediated vasodilation and amplification of the i mmune response, respectively.