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Lack of Syndecan-1 Enhances Interaction Between Leukocytes and Endothelial Cells
1Peters S., 1Radetzky S., 2Götte M., 3Bernfield M., 1Joussen A. M.,
1Universität zu Köln, Zentrum für Augenheilkunde, Abteilung für Netzhaut- und Glaskörperchirurgie (Köln)
2Westfälische Wilhelms-Universität Münster, Institut für Biochemie (Münster)
3Children`s Hospital, Harvard Medical School (Boston)
Purpose: Leukocyte-endothelial interactions play an important role in angiogenesis as well as in vascular diseases as non-proliferative diabetic retinopathy or uveitis. Leukocyte adhesion to the endothelium and following extravasation during inflammation is mediated by cell surface molecules like selectins, cell adhesion molecules, integrins and chemokines. The present study investigates the influence of Syndecan-1 a heparan sulfate proteoglycan binding and modyfying these cell surface molecules on the leukocyte-endothelial interaction.
Method: Syndecan-1-knockout mice (sdc -/-) were perfused with FITC-coupled Concavalin-A lectin, which stains for adherent leukocytes and endothelial cells. Retinal and experimentally induced corneal vessels were examined.
Results: Syndecan-1-knockout mice show an increased adhesion of leukocytes to the endothelium. Intravital microscopy demonstrated, that pretreatment with TNFa enhanced this adhesion even more, compared to wild type mice. Experimentally induced corneal angiogenesis was enhanced in sdc -/- mice.
Conclusions: Syndecan-1 reduces leukocyte-mediated inflammatory responses. Lack of Syndecan-1 may attribute to the increased corneal angiogenesis in sdc-/- mice. Syndecan-1 may be a target for prevention of leukocyte-endothelial interactions in angiogenesis and inflammatory diseases of the eye.