The role of proteoglycans regulation of airways inflammation and airways remodelling

Proteoglycans such as heparin have been recognized as useful anticoagulant drugs for a long time. However, it is now apparent that proteoglycans posse ss a wide array of biologic activities that are of potential interest in ou r understanding of the regulation of airways inflammation and remodelling i n addition to their anticoagulant effects.(1) A proteoglycan is any glycopr otein that consists of a protein core and has glycosaminoglycan side chains . Glycosaminoglycans are polysaccharides that have a simple repeating disac charide unit and are highly anionic in nature because of the presence of ma ny sulphate and carboxyl groups.(2) Heparin is found exclusively in mast ce ll granules in mammals,(3) whereas heparan sulphate is ubiquitous, being fo und on the surface of must cell types, particularly on the surface of vascu lar endothelial cells.(1) However, although we have known for some time tha t heparin is present in mast cell granules, where it binds histamine and th e mast cell enzymes, tryptase, and chymase,(3) little is known about the ro le of endogenous heparin. It is now clear that after the exposure of human lung mast cells to house dust-mite allergen, heparin can be released into t he extracellular environment.(4) This article will review the biologic acti vities of heparin and related proteoglycans that are of interest in the con text of our understanding of airway inflammation and remodelling.