[Frontiers in Bioscience 14, 4932-4949, June 1, 2009]

Heparan sulfate proteoglycans in extravasation: assisting leukocyte guidance

Johanna W.A.M. Celie1, Robert H.J. Beelen1, Jacob van den Born2

1Department of Molecular Cell Biology & Immunology, VU University Medical Center, P.O. box 7057, 1007MB, Amsterdam, 2Department of Nephrology, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, the Netherlands

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. HSPG structure, biosynthesis and protein binding properties
4. HSPGs on the endothelium - sticky or not
4.1. Anti-adhesive HSPGs in the non-inflamed endothelial glycocalyx
4.2. HSPGs on the inflamed endothelium: interaction with L-selectin
4.3. Other adhesive interactions with endothelial HSPGs
5. HSPGs and chemokines: selective presentation
5.1. HSPGs present chemokines to facilitate directional migration
5.2. Chemokine presentation by HSPGs at the endothelial surface
6. Beyond the endothelium: HSPGs in the vascular basement membrane
7. HSPGs on leukocytes
8. Regulation of HSPGs upon inflammation
8.1. Regulation of core protein expression
8.2. Regulation of HS biosynthesis & modification; changes that affect chemokine/L-selectin binding
9. HSPGs as therapeutics or targets in anti-inflammatory strategies
10. Conclusions and Perspectives
11. Acknowledgments
12. References

1. ABSTRACT

Heparan sulfate proteoglycans (HSPGs) are glycoconjugates that are implicated in various biological processes including development, inflammation and repair, which is based on their capacity to bind and present several proteins via their carbohydrate side chains (glycosaminoglycans; GAGs). Well-known HSPGs include the family of syndecans and glypicans, which are expressed on the plasma membrane and perlecan, agrin and collagen type XVIII, which are present in basement membranes. In this review, we provide an overview of the current knowledge on the role and regulation of HSPGs in leukocyte extravasation. In the non-inflamed endothelial glycocalyx HSPGs are anti-adhesive, and there are several indications that active regulation of HSPG core protein expression and/or GAG modification occurs upon inflammation. We address the current evidence for the role of HSPGs in leukocyte extravasation through interaction with the leukocyte adhesion molecule L-selectin, chemokines and other binding partners. Finally, a number of possibilities to use HSPGs as therapeutics or targets in anti-inflammatory strategies are discussed.