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

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

Research output: Contribution to journalArticle

47 Citations (Scopus)

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 - 2002
Externally publishedYes

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Low Molecular Weight Heparin
Cell Adhesion
Cell Movement
T-Lymphocytes
Chemokine CCL21
Glycosaminoglycans
Chemotaxis
Heparin Lyase
Aptitude
Chemokines
Autoimmune Diseases
Heparin
Leukocytes
Pathology
Inflammation
Enzymes

ASJC Scopus subject areas

  • Pharmacology

Cite this

Low-molecular-weight heparins inhibit CCL21-induced T cell adhesion and migration. / Christopherson, Kent W.; Campbell, James J.; Travers, Jeffrey; Hromas, Robert A.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 302, No. 1, 2002, p. 290-295.

Research output: Contribution to journalArticle

Christopherson, Kent W. ; Campbell, James J. ; Travers, Jeffrey ; Hromas, Robert A. / Low-molecular-weight heparins inhibit CCL21-induced T cell adhesion and migration. In: Journal of Pharmacology and Experimental Therapeutics. 2002 ; Vol. 302, No. 1. pp. 290-295.
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