PMID- 15020655
OWN - NLM
STAT- MEDLINE
DCOM- 20040712
LR  - 20121115
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 75
IP  - 6
DP  - 2004 Jun
TI  - Heparin-disaccharide affects T cells: inhibition of NF-kappaB activation, cell 
      migration, and modulation of intracellular signaling.
PG  - 1139-46
AB  - 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 alpha 
      (TNF-alpha), interleukin (IL)-8, and IL-1beta] 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-kappaB activity and reduced the secretion of TNF-alpha and 
      interferon-gamma (IFN-gamma) by anti-CD3-activated T cells. In addition, 3S-DS 
      inhibited CXC chemokine ligand 12 (CXCL12; stromal cell-derived 
      factor-1alpha)-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 of 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.
FAU - Hecht, Iris
AU  - Hecht I
AD  - Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, 
      Israel.
FAU - Hershkoviz, Rami
AU  - Hershkoviz R
FAU - Shivtiel, Shoham
AU  - Shivtiel S
FAU - Lapidot, Tzvi
AU  - Lapidot T
FAU - Cohen, Irun R
AU  - Cohen IR
FAU - Lider, Ofer
AU  - Lider O
FAU - Cahalon, Liora
AU  - Cahalon L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040312
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (Disaccharides)
RN  - 0 (Fibronectins)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (heparin disaccharide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9005-49-6 (Heparin)
RN  - 9050-30-0 (Heparitin Sulfate)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 2)
RN  - EC 2.7.10.2 (Ptk2b protein, mouse)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Bone Marrow/metabolism
MH  - Cell Adhesion/drug effects
MH  - Cell Movement/*drug effects
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/metabolism
MH  - Chemotaxis
MH  - Disaccharides/*pharmacology
MH  - Fibronectins/metabolism
MH  - Focal Adhesion Kinase 2
MH  - Heparin/*analogs & derivatives/*pharmacology
MH  - Heparitin Sulfate/pharmacology
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/antagonists & inhibitors/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Receptors, CXCR4/metabolism
MH  - *Signal Transduction
MH  - T-Lymphocytes/*drug effects/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2004/03/17 05:00
MHDA- 2004/07/13 05:00
CRDT- 2004/03/17 05:00
PHST- 2004/03/17 05:00 [pubmed]
PHST- 2004/07/13 05:00 [medline]
PHST- 2004/03/17 05:00 [entrez]
AID - jlb.1203659 [pii]
AID - 10.1189/jlb.1203659 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2004 Jun;75(6):1139-46. doi: 10.1189/jlb.1203659. Epub 2004 Mar 
      12.