Immunohistochemical localization of vascular endothelial growth factor in colonic mucosa of patients with inflammatory bowel disease.
OBJECTIVE
Significantly enhanced serum levels of VEGF (vascular endothelial growth factor) were found in patients with inflammatory bowel disease. Peripheral blood mononuclear cells have been identified as one of the origins of the circulating VEGF. The present investigation examines the localization of VEGF at the site of inflammation in colonic mucosa of patients with Crohn's disease and ulcerative colitis.


METHODS
Immunohistochemical localization of VEGF and immunostaining for leukocytes were performed in colonic mucosal biopsies of 41 patients with Crohn's disease, 26 patients with ulcerative colitis and normal mucosal specimens of 5 patients with irritable bowel syndrome. Measurement of immunohistochemical staining for VEGF and for leukocytes within the epithelium and the lamina propria was performed separately by area morphometry using a computerized cell analysis system.


RESULTS
In both patients with Crohn's disease and ulcerative colitis immunohistochemical staining for VEGF within the lamina propria of inflamed colonic mucosa was significantly higher compared with noninflamed mucosa (Crohn's disease: 4.26% vs. 0.07%, P < 0.001; ulcerative colitis: 3.68% vs. 0.32%, P = 0.001). There was a significant correlation between immunostaining for leukocytes and VEGF within the lamina propria in both patients with Crohn's disease (r = 0.73, P < 0.05)) and ulcerative colitis (r = 0.67, P < 0.05). In Crohn's disease immunostaining for VEGF within the epithelium was significantly higher in inflamed mucosa compared with noninflamed mucosa (9.85% vs. 0.63%, P < 0.001). In contrast, strong immunostaining for VEGF has been observed in the epithelium of noninflamed mucosa (7.60%, P < 0.003), as well as in inflamed mucosa of patients with active ulcerative colitis (9.68%, P < 0.002) compared with noninflamed mucosa of patients with inactive ulcerative colitis (1.39%).


CONCLUSIONS
The present data indicate, that the increased VEGF expression within the epithelium and the interstitial accumulation of VEGF-producing leukocytes in inflamed mucosa may play an important role in the inflammatory mechanisms of Crohn's disease and ulcerative colitis.
Griga
Thomas
T
Department of Gastroenterology, University Hospital Bergmannsheil, Bürkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany. thomas.griga@ruhr-uni-bochum.de
May
Burkard
B
Pfisterer
Okka
O
Müller
Klaus-Michael
KM
Brasch
Frank
F
D000328:Adult; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003106:Colon; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors