Heparin, cell adhesion, and pathogenesis of inflammatory bow el disease

Tissue repair involves a close interplay between growth factors and cell adhesion molecules. The normal healing process may be disrupted by pathophysiological states such as inflammation, due to loss of growth factors, cell adhesion molecules, or both, which results in a reduced rate of healing. Such events may occur in inflammatory bowel disease during mucosal restitution. We postulate that the beneficial response to heparin observed in inflammatory bowel disease may result from mechanisms in addition to anticoagulation. These include the restoration of high-affinity receptor binding by antiulcerogenic growth factors, such as basic fibroblast growth factor, that normally rely on the presence of heparan sulphate proteoglycans, such as syndecan-1, as coreceptors. Loss of syndecan-1 has been observed in the ulcerated mucosa of patients with inflammatory bowel disease. This loss may lead to impaired binding of basic fibroblast growth factor and a reduced rate of ulcer healing. We suggest that heparin restores high-affinity receptor binding of basic fibroblast growth, and so increases the rate of mucosal recovery.