Low-molecular-weight heparins inhibit CCL21-induced T cell adhesion and migration

Kent W. Christopherson, James J. Campbell, Jeffrey B. Travers, Robert A. Hromas

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)290-295
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume302
Issue number1
DOIs
StatePublished - Jul 4 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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