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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2343-2349. Prepublished online as a Blood First Edition Paper on October 21, 2004; DOI 10.1182/blood-2004-08-3140. This Article Full Text (PDF) All Versions of this Article: 2004-08-3140v1 105/6/2343    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhu, K. Articles by Koch, A. E Search for Related Content PubMed PubMed Citation Articles by Zhu, K. Articles by Koch, A. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 25, 2004 Accepted October 13, 2004 Mechanism by which H-2g, a glucose analog of blood group H antigen, mediates angiogenesis Kui Zhu, M A Amin, Yuanyuan Zha, Lisa A Harlow, and Alisa E Koch* Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Veterans Administration Chicago Healthcare System, Lakeside Division, Chicago, IL, USA; Division of Rheumatology, University of Michigan, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, MI, USA * Corresponding author; email: aekoch{at}med.umich.edu. The 4A11 antigen is a unique cytokine inducible antigen upregulated on rheumatoid arthritis (RA) synovial endothelial cells (ECs) compared to normal ECs. Previously, we showed that in soluble form, this antigen, Lewisy-6/H-5-2 (Ley/H) or its glucose analog, 2-fucosyl lactose (H-2g), induced the expression of EC intercellular adhesion molecule-1 (ICAM-1) and leukocyte-endothelial adhesion through the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway. Currently, we show that H-2g induces release of EC angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), an effect inhibited by decoy NFB oligodeoxynucleotide (ODN). JAK2 and phosphoinositide-3 kinase (PI3K) are two upstream kinases of NFB activated by H-2g, as confirmed by an IKK assay. In vitro, H-2g induces vascular sprouting in the rat aortic ring model, while blockade of JAK2, PI3K or NFB inhibits sprouting. Likewise, in the in vivo mouse Matrigel plug angiogenesis assay, chemical inhibitors and antisense or decoy ODNs of JAK2, PI3K or NFB decrease angiogenesis, confirming the importance of these pathways in H-2g induced EC signaling. The critical role of Ley/H involvement in angiogenesis and its signaling pathways may provide new targets for therapy of diseases characterized by pathological neovascularization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Y. Cheranov, M. Karpurapu, D. Wang, B. Zhang, R. C. Venema, and G. N. Rao An essential role for SRC-activated STAT-3 in 14,15-EET-induced VEGF expression and angiogenesis Blood, June 15, 2008; 111(12): 5581 - 5591. [Abstract] [Full Text] [PDF]

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