Heparin-disaccharide affects T cells: Inhibition of NF-κB activation, cell migration, and modulation of intracellular signaling

Iris Hecht, Rami Hershkoviz, Shoham Shivtiel, Tzvi Lapidot, Irun R. Cohen, Ofer Lider*, Liora Cahalon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


We previously reported that disaccharides (DS), generated by enzymatic degradation of heparin or heparan sulfate, inhibit T cell-mediated immune reactions in rodents and regulate cytokine [tumor necrosis factor α (TNF-α), interleukin (IL)-8, and IL-1β] secretion by T cells, macrophages, or intestinal epithelial cells. Here, we investigated the effects of a trisulfated heparin DS (3S-DS) on two aspects of T cell function: secretion of proinflammatory cytokines and migration to an inflamed site. 3S-DS down-regulated nuclear factor-κB activity and reduced the secretion of TNF-α and interferon-γ (IFN-γ) by anti-CD3-activated T cells. In addition, 3S-DS inhibited CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor-1α)-dependent migration in vitro and in vivo and decreased CXCL12-induced T cell adhesion to the extracellular matrix glycoprotein, fibronectin (FN). This inhibition was accompanied by attenuation of CXCL12-induced Pyk2 phosphorylation but did not involve internalization of the CXCL12 receptor, CXCR4, or phosphorylation or extracellular-regulated kinase. Despite inhibiting CXCL12-induced adhesion, 3S-DS, on its own, induced T cell adhesion to FN, which was accompanied by phosphorylation of Pyk2. A monosulfated DS showed no effect. Taken together, these data provide evidence that 3S-DS can regulate inflammation by inducing and modulating T cell-signaling events, desensitizing CXCR4, and modulating T cell receptor-induced responses.

Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalJournal of Leukocyte Biology
Issue number6
StatePublished - Jun 2004


  • CXCL12
  • Chemokines
  • Extracellular matrix
  • IFN-γ
  • TNF-α-


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