Le(y)/H: An endothelial-selective, cytokine-inducible, angiogenic mediator

Endothelial cells (ECs) are key participants in angiogenic processes that c haracterize tumor growth, wound repair, and inflammatory diseases, such as human rheumatoid arthritis (RA). We and others have shown that EC molecules , such as soluble E-selectin, mediate angiogenesis. Here me describe an EC molecule, Lewis(y)-6/H-5-2 glycoconjugate (Le(y)/H), that shares some struc tural features with the soluble E-selectin ligand, sialyl Lewis(x) (sialyl Le(x)). One of the main previously recognized functions of Lewis(y) is as a blood group glycoconjugate. Here me show that Le(y)/H is rapidly cytokine inducible, up-regulated in RA synovial tissue, where it is cell-bound, and up-regulated in the soluble form in angiogenic RA compared with nonangiogen ic osteoarthritic joint fluid, Soluble Le(y)/H also has a novel function, f or it is a potent angiogenic mediator in both in vitro and in vivo bioassay s. These results suggest a novel paradigm of soluble blood group Ags as med iators of angiogenic responses and suggest new targets for therapy of disea ses, such as RA, that are characterized by persistent neovascularization.