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GF Roessler, M Goette, AP Adamis, M Bernfield, B Kirchhof, AM Joussen; Lack of Syndecan-1 Promotes Leukocyte - Endothelial Interactions in the Ocular Vasculature . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2749.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Leukocyte endothelial interactions are a key feature of ocular angiogenesis, but also play a role in non-proliferative vascular alterations as found in early diabetes or uveitis. The adhesion of leukocytes to endothelial cells during inflammation is a multistep process that involves leukocyte rolling, adhesion and extravasation mediated by selectins, cell adhesion molecules (CAM's), integrins and chemokines. Heparan sulfate (HS) is known to bind to and modify the function of these molecules under physiological conditions. Here we investigate the role of the HS-proteoglycan syndecan-1 in mediating leukocyte-endothelial interactions in the ocular vasculature. Methods: We used mice carrying a deletion in the gene encoding the cell surface heparan sulfate proteoglycan syndecan-1 (sdc1) to study the interactions of leukocytes and endothelial cells in vivo using a perfusion technique with FITC-coupled Concanavalin A. Results: sdc1 -/- mice show an increased leukocyte adhesion in a retina perfusion model, which could be largely attributed to the leukocytes. Intravital microscopy studies revealed a dramatic increase in adhesion following tumor necrosis factor a (TNFa) treatment of sdc1 -/- mice compared to similarly treated wild-type mice. The higher degree of leukocyte adhesion might account for an increase in inflammation-mediated corneal angiogenesis observed in sdc1 -/- mice. Conclusion: Our results indicate a role for syndecan-1 as a negative regulator of leukocyte-mediated inflammatory responses. Thus, syndecan-1 could be potentially used as a target for prevention of pathological leukocyte-endothelial interactions in angiogenesis and inflammation.
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