Anti-P-Selectin Antibody Exacerbated Inflammatory Responses in Acetic Acid-Induced Colitis

The emigration of leukocytes from the vascular compartment to the site of injury is a key event in the development of inflammation. This transendothelial emigration of leukocytes is a complex series of events involving the expression and function of several adhesion molecules. The series of steps is started by tethering of leukocytes to the endothelium which initiates rolling, this in turn activates the leukocytes and leads to firm adherence and transendothelial migration1. The use of specific antibodies to particular adhesion molecules has been reported to reduce the inflammatory response in ischemia/reperfusion injury2, 3 and acute lung injury4. Increased expression of intercellular adhesion molecule-1 (ICAM-1), and its counter receptors the integrins LFA-1 and Mac-1 has been reported in mucosal biopsies of patients with IBD5. We have demonstrated, that monoclonal antibodies to ICAM-1 (1A29) greatly ameliorated the inflammatory response in rats, seven days after acetic acid (6%) administration6. In this communication, we report the role of P-selectin on early inflammatory response in acetic acid-induced colitis in rats. Expression of P-selectin is believed to be critical in the tethering of leukocytes to vascular endothelium and subsequent rolling1. In addition, P-selectin expression is increased in activated platelets where it mediates leukocyte-platelet adhesion7. In-vivo, selectin has been reported to be involved in lactoferrin induced intestinal mucosal injury8, splanchnic ischemia-reperfusion3 and acute lung injury4. P-selectin is stored in intracellular granules in endothelial cells (and platelets). It can be mobilized to the plasma membrane within minutes of activation of endothelial cells by thrombin, histamine and oxygen radicals or peroxides9, 10.