TY - JOUR T1 - Low-Molecular-Weight Heparins Inhibit CCL21-Induced T Cell Adhesion and Migration JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 290 LP - 295 DO - 10.1124/jpet.302.1.290 VL - 302 IS - 1 AU - Kent W. Christopherson II AU - James J. Campbell AU - Jeffrey B. Travers AU - Robert A. Hromas Y1 - 2002/07/01 UR - http://jpet.aspetjournals.org/content/302/1/290.abstract N2 - The chemokine CCL21, also known as Exodus-2/6-Ckine/secondary lymphoid-tissue chemokine/T cell activator protein-4, is the most potent stimulator of T cell migration and adhesion yet described. Endothelial heparin-like glycosaminoglycans (GAGs) are thought to present chemokines at sites of inflammation, maintaining a local concentration gradient to which leukocytes can respond. In contrast, this study found that GAGs markedly inhibit the ability of CCL21 to stimulate T cell adhesion and chemotaxis. Enzymes, such as heparinase, that split GAGs into component-sulfated saccharides abrogate this inhibition, suggesting a mechanism for local tissue regulation of CCL21 function. Low-molecular-weight heparins also strongly inhibit CCL21 adhesion and chemotaxis. Therefore, low-molecular-weight heparins may be effective therapeutic agents in decreasing the pathology of T cell-infiltrative autoimmune diseases by targeting the CCL21 regulation of T cell infiltration. The American Society for Pharmacology and Experimental Therapeutics ER -