Deficiency of epithelial basement membrane laminin in ulcerative colitis affected human colonic mucosa

Imbalances in epithelium-matrix interactions have been discussed as a patho mechanism in ulcerative colitis, causing a colonic mucosal barrier dysfunct ion. Laminin. the major noncollagenous component of the basement membrane, plays a role in epithelial basal lamina formation and promotes differentiat ion of human enterocytes. We therefore investigated the distribution of lam inin in ulcerative colitis affected colonic tissues. Tissue specimens from both affected and nonaffected colonic regions were obtained from ten patien ts with ulcerative colitis during colonoscopies or operations. Healthy tiss ue from five patients with colorectal cancer was used as control. After his tological classification, the localization and distribution of the basement membrane associated extracellular matrix proteins were determined by immun ohistochemistry. Paraffin-embedded sections were incubated with antibodies against laminin and type IV and V collagen. No positive immunoreactivity ag ainst laminin was found in most of the epithelial basement membranes surrou nding the crypts in affected colonic tissues, without involvement of the su bendothelial structures. In contrast, a type IV and V collagen accumulation occurred in all these tissue samples. The lack of laminin in combination w ith an overexpression of type IV and V collagen, as reported for the first time in this paper, leads to changes in basement membrane structure. These findings indicate that the three-dimensional network of the colonic epithel ial basement membrane and its function are seriously disturbed in exacerbat ing ulcerative colitis. This provides new insights into the importance of c ell-matrix interactions for physiological and pathological mechanisms in th e etiology of ulcerative colitis.