Author(s): Ferro V
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Abstract INTRODUCTION: Heparan sulfate (HS) is a polysaccharide that is ubiquitously expressed on the cell surface and in the extracellular matrix and interacts with a wide variety of proteins to mediate numerous biological and pathological functions, including inflammation. AREAS COVERED: The structural diversity and the multiple biological roles of HS in inflammation are discussed. HS is involved in the recruitment and attachment of leukocytes to the inflamed epithelium, the activation of chemokines and the transmigration of leukocytes to the underlying target tissue. The endoglycosidase heparanase plays a key role in the above processes via the degradation of HS. HS mimetics that inhibit heparanase and block HS-binding proteins have been shown to inhibit inflammation in multiple animal models. EXPERT OPINION: HS plays important roles in many stages of the inflammation process, in particular the regulation of leukocyte extravasation. Compounds that can inhibit HS-protein interactions thus have considerable potential as anti-inflammatory therapeutics capable of simultaneously interfering with multiple steps of the inflammation process. There are a number of such compounds in various stages of clinical development for cancer, which should also find applications in inflammatory illnesses.
This article was published in Expert Opin Ther Targets
and referenced in Journal of Clinical & Cellular Immunology