ICAM-1 antibodies reduce leukocyte adherence and -extravasation in DSS-induced colitis in mice: assessment by in vivo fluorescence microscopy

Introduction: Leuko cyte-endothelial interactions play a pivotal role in th e pathogenesis of inflammatory bowel disease (IBD). In addition recent rese arch suggest an important role for the adhesionmolecule ICAM-1 in intestina l inflammation. Therefore we investigated the effect of an monoclonar antib ody against ICAM-1 on leukocyte adherence and extravasation in colitis usin g in vivo fluorescence microscopy. Material and methods: Colitis was established in Balb C mice by DSS (Dextra n Sodium Sulfate) application. Controls received isotyp control antibody, t he experimental group anti ICAM-1 antibody. In vivo microscopy was performe d after mobilizing the colon and in vivo labelling of leukocytes venule of the colon was calculated. After antimesenteric incision the number of extra vasated leukocytes in the mucosa was counted ICAM-1 expression was demonstr ated by immunhistochemistry. Results: ICAM-1 expression was increased in DSS-induced colitis. Treatment with anti ICA M-l antibody reduced leukocyte adherence in submucosal postca pillary and collecting venules and leukocytes extravasation in the mucosa c ompared to controls. Summary and Conclusion: We demonstrated increased ICAM-1 expression in DSS- induced colitis in mice. Using in vivo microscopy, we further were able to show that a monoclonal antibody against ICAM-1 significantly reduces leukoc yte adherance and extravasation in DSS-induced colonic inflammation. The re sults support not only the therapeutical concept of ICAM-1 suppression in I BD [2] but also establish the method of in vivo microscopy as a new tool fo r the evaluation of experimental therapies in colonic : inflammation.