Obliterative arteritis with nitric oxide synthase and HLA-DR expression in Crohn's colitis.
OBJECTIVE
To cast light on whether inflammatory vascular injury is a possible pathogenic mechanism in Crohn's disease, the histological characteristics of vascular lesions were investigated.


METHODS
Affected vessels in surgically resected colons from 23 patients 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 oxid synthase, vascular endothelial growth factor and E-cadherin.


RESULTS
Inflammatory-cell infiltrates affecting arteries, accompanied by obliterative 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 positively correlated with the degree of obliterative arteritis. Granulomatous vasculitis was found exclusively in Crohn's disease (10 cases; 43.5%). In addition, focally enhanced endothelial staining of HLA-DR, with expression in granulomas adjacent to vessels was occasionally observed. In the endothelium 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 and controls (P < 0.05-0.01). In the involved arteries, enhanced endothelial nitric oxide synthase expression was most common in Crohn's disease among the groups (P < 0.05). A few cases of Crohn's disease, ulcerative colitis and ischemic colitis were positive for inducible nitric oxide synthase, vascular endothelial growth factor or E-cadherin in the vessel walls.


CONCLUSIONS
The presence of characteristic obliterative arteritis and granulomatous vasculitis, a possible cause of ischemic injury, supports, in part, a vascular hypothesis for the pathogenesis of Crohn's disease. Enhanced expression of endothelial nitric oxide synthase and HLA-DR possibly reflects compensatory endothelium-mediated vasodilation and amplification of the immune response, respectively.
Yokoyama
K
K
Department of Internal Medicine, School of Medicine, Kitasato University East Hospital, 2-1-1 Asamizo-dai, Sagamihara, Kanagawa 228-8520, Japan.
Mitomi
H
H
Kobayashi
K
K
Katsumata
T
T
Saigenji
K
K
Okayasu
I
I
D000328:Adult; D001167:Arteritis / Q000378:metabolism / Q000473:pathology*; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology*; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D006684:HLA-DR Antigens; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III