Heparin Regulation of the Complement System

The complement system consists of approximately 25 proteins that work to complement the activity of antibodies in destroying bacteria, either by facilitating phagocytosis or by puncturing the bacterial cell membrane resulting in bacterial cell lysis (1). Heparin, a clinically used anticoagulant, is a polydisperse, highly sulfated, linear polysaccharide consisting of 1!4 linked uronic acid and glucosamine residues (2,3). The biological activities of pharmaceutical heparin are reviewed elsewhere (2–6). Heparin can bind to a variety of proteins, including growth factors (7), proinflammatory chemokines and cytokines (6), extracellular matrix proteins (8), and complement proteins (9). Binding takes place primarily through electrostatic interactions between heparin’s anionic groups (sulfo and carboxyl), and the positively charged amino acid residues (arginine and lysine) of the heparin-binding proteins (10,11). Heparin–protein interactions regulate such diverse processes as coagulation, homeostasis (12), cell adhesion (8), lipid metabolism (13), growth factor signal Garg / Chemistry and Biology of Heparin and Heparan Sulfate chap11 Revise Proof page 313 8.11.2005 12:44pm