Heparin also interacts with selectins and modulates the cell adhesion process.

Modulates the Cell Adhesion Process To the Editor: We read with great interest the article by Peter and coworkers1 in the October 5, 1999 issue of Circulation in which the authors demonstrated the binding of heparin to integrin Mac-1 on stimulated leukocytes. Recent investigations have revealed that heparin can modulate biological processes, such as binding to adhesion receptors on endothelial cells and leukocytes.2 Leukocyte adhesion is a complex molecular process, and multiple adhesion receptor systems mediate the recruitment of leukocytes from the blood. The initial trafficking of circulating leukocytes to sites of inflammation is mediated by the selectin family of adhesion receptors; this is followed by the engagement of additional cellular recognition receptors, including the immunoglobulin superfamily and integrins. Heparin interacts with adhesion molecules, including integrin Mac-1 (CD11b/CD18) and selectins.3,4 Peter and colleagues speculated that the binding of heparin to Mac-1 and the consequent inhibition of Mac-1 ligand binding could directly modulate coagulation, inflammation, and cell proliferation. They failed to mention the role of other adhesion molecules, such as selectins, in this process. We would like to bring to the authors’ attention our study on the role of heparin in the cell adhesion process.5 This study revealed that heparin inhibits leukocyte adhesion by antagonizing the function of selectins. We evaluated the efficacy of sulfated polysaccharides (unfractionated heparin, low-molecular-weight heparin, heparan sulfate, chondroitin sulfate, and dextran sulfate) on leukocyte accumulation in the infarcted brain and found that the administration of these sulfated polysaccharides led to reduced leukocyte accumulation. The relative potency of leukocyte accumulation inhibition of the sulfated polysaccharides tested was as follows: dextran sulfate $ unfractionated heparin . low-molecularweight heparin $ chondroitin sulfate $ heparan sulfate. Potency was correlated with the molecule’s degree of sulfation. We hypothesized that leukocyte recruitment was due to an interaction between leukocyte selectins and carbohydrate ligands, such as the sulfated polysaccharide side chains of proteoglycans on the endothelial cell surface. Therefore, in addition to integrin Mac-1, selectins also play an important role in the cell adhesion process, and this promiscuous binding of heparin may modulate inflammation and cell proliferation.