INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION IN DEXTRAN SODIUM SULFATE-INDUCED COLITIS IN RATS

Orally administered dextran sodium sulfate (DSS) produces an acute col itis in rodents. The pathogenesis is unknown but may relate to DSS-med iated toxicity of colonic crypt epithelium and/or DSS-induced inflamma tion. The purpose of this study was to determine when colonic mucosal inflammation, as indicated by histopathology and intercellular adhesio n molecule-1 (ICAM-1) expression, occurs relative to crypt epithelial damage. Groups of eight adult male Wistar rats were administered 5.0% DSS solution in the drinking water for 2-6 days. Clinical signs at 3 d ays consisted of loose stool, progressing to marked rectal hemorrhage by days 5 and 6 that correlated with marked intraluminal colonic hemor rhage at necropsy. Histological lesions of predominantly the distal co lon consisted of multifocal areas of mucosal erosion, reduction in gob let cells, dilated crypts, crypt collapse, increased lamina propria ne utrophils, and submucosal edema on days 2 and 3, progressing to locall y extensive ulceration and marked mixed inflammatory infiltrates by da ys 4-6. Enhanced expression of ICAM-1, demonstrated by both immunohist ochemical and northern blot analysis, was evident in colonic mucosa as early as day 2, with consistent increases through days 3-6. Results d emonstrate that enhanced colonic mucosal endothelial cell ICAM-1 expre ssion is an early event in the inflammatory cascade of DSS-induced col itis.