Development of effective inhibitors against carbohydrate recognition adhesion molecules involved in invasion of inflammatory cells and/or cancer cells.

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1. We have for the first time succeeded in identifying versican as a ligand for a leukocyte adhesion molecule, L-selectin. Versican is a large chondrotin sulfate proteoglycan produced by fibroblasts. Unlike other ligands for L-selectin, versican is not modified with sialyl Lewis X type carbohydrates, but has chondroitin sulfate side chains which interacts with the lectin domain of L-selectin. Versican is localized in epithelial cells of distal tubules of the kidney under physiological conditions, but is rapidly released from there under pathological conditions. The shed versican is then recognized by leukocyte L-selectin, which may promote tissue injury.2. Versican can bind to not only L-selectin but also other inflammatory adhesion molecules, such as P-selectin and CD44. In addition, it can capture a certain type of chemokines on its chondrotin sulfate side chains, which may result in augmenting inflammatory responses. It was revealed that functional inhibition of L-selectin leads to inhibition of interstitial nephritis induced by ureteral obstruction.3. We have found a substance that can inhibit fucosylation and sialylation of cell surface proteins.