FUNCTION OF THE SELECTIN FAMILY AND FUNDAMENTAL STUDY ON THE DEVELOPMENT OF A NEW DRUGS FOR ANTI-INFLAMMATION AND ANTI-TUMOUR MATASTASIS

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In this project years (1995-1996), we found new selectin ligands, sulfated sugar chains, such as sulfatide, and several kinds of sulfated oligosaccharides (sulfated chitin, sulfated hyaluronic acid, etc.). Sulfatide, isolated from brain, a sulfated galactosylc eramide is a potential ligand for L- and P-selectins, which binds specifically L- and P-selectins but not to E-selectin. Divalent cations were not necessary for the binding of sulfatide to L- and P-selectins. These properties are different from SLex which has been identified as a common ligand for L-, P-, and E-selectins. We found that the sulfatide blocks strongly cobra venom factor-induced lung injury which is identified as an L- and P-dependent lung inflammation. Sulfatide also blocked mononuclear cell infiltration into the kidney interstitium induced by tublar injury following ureteral obstruction, which is identified as one of the L-selectin-dependent kidney inflammation. Sulfatide also blocked the lung metastasis of the B-16 melanoma cells. Sulfatide was selectively expressed on B cells, but not on T cells, and also inhibited the B cell proliferation and Ig production. These results suggested a novel role of the L-selectin/its ligand system in the initiation of B cell activation and antibody production.The results obtained in the project years may potentially be applied for the development of a new drugs for the anti-infmammation and anti-tumor cell metastasis.