PMID- 9497493
OWN - NLM
STAT- MEDLINE
DCOM- 19980317
LR  - 20190512
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 92
IP  - 4
DP  - 1997 Dec
TI  - Endothelial production of MCP-1: modulation by heparin and consequences for 
      mononuclear cell activation.
PG  - 512-8
AB  - Heparin is a polyanionic glycosaminoglycan (GAG) that can bind with high affinity 
      to a range of cytokines including interferon-gamma (IFN-gamma) and members of the 
      chemokine superfamily. This GAG also possesses immunomodulatory activity in vivo 
      and can antagonize the capacity of IFN-gamma to induce class II MHC antigen 
      expression, and to up-regulate intercellular adhesion molecule-1, by cultured 
      endothelial cells. Previous studies have shown that binding to cell-surface 
      heparan sulphate is essential for optimal activity of IFN-gamma and that free 
      heparin competitively inhibits this sequestration process. The present study was 
      performed to increase our understanding of the immunosuppressive activity of 
      heparin by investigation of potential antagonism of the production and function 
      of monocyte chemotactic peptide-1 (MCP-1), a chemokine important for mononuclear 
      leucocyte recruitment across vascular endothelium. It was found that mixture of 
      heparin with IFN-gamma inhibited up-regulation of the signal transducer and 
      activator of transcription protein, STAT-1 produced normally by treatment of 
      endothelial cells with IFN-gamma. An inhibition of MCP-1 production was observed 
      that was specifically caused by mixture of IFN-gamma with heparin-like, and 
      therefore cytokine-binding, GAGs. It was also shown that mixture of heparin-like 
      GAGs with MCP-1 inhibited the rapid tyrosine phosphorylation of 
      phosphatidylinositol 3-kinase which is normally produced by treatment of 
      mononuclear leucocytes with this chemokine. Blockade of this intracellular 
      signalling event was associated with a reduction in the normal transendothelial 
      migration response towards MCP-1. Results from this study indicate that soluble, 
      heparin-like GAGs can block IFN-gamma-dependent up-regulation of MCP-1 production 
      by cultured endothelial cells, and can also antagonize the leucocyte-activating 
      and migration-promoting properties of pre-existing MCP-1. These activities may 
      contribute to the immunomodulatory properties of heparin.
FAU - Douglas, M S
AU  - Douglas MS
AD  - Department of Surgery, University of Newcastle, Newcastle upon Tyne, UK.
FAU - Ali, S
AU  - Ali S
FAU - Rix, D A
AU  - Rix DA
FAU - Zhang, J G
AU  - Zhang JG
FAU - Kirby, J A
AU  - Kirby JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (Trans-Activators)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Blotting, Western
MH  - Cell Culture Techniques
MH  - Chemokine CCL2/antagonists & inhibitors/*biosynthesis
MH  - DNA-Binding Proteins/metabolism
MH  - Endothelium, Vascular/*immunology
MH  - Glycosaminoglycans/pharmacology
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Interferon-gamma/immunology
MH  - Leukocytes, Mononuclear/*drug effects/immunology
MH  - Lymphocyte Activation/drug effects
MH  - Lymphocyte Culture Test, Mixed
MH  - Recombinant Proteins
MH  - STAT1 Transcription Factor
MH  - Signal Transduction/drug effects
MH  - Trans-Activators/metabolism
MH  - Up-Regulation/drug effects
PMC - PMC1364157
EDAT- 1998/03/14 00:00
MHDA- 1998/03/14 00:01
PMCR- 1998/12/01
CRDT- 1998/03/14 00:00
PHST- 1998/03/14 00:00 [pubmed]
PHST- 1998/03/14 00:01 [medline]
PHST- 1998/03/14 00:00 [entrez]
PHST- 1998/12/01 00:00 [pmc-release]
AID - 10.1046/j.1365-2567.1997.00385.x [doi]
PST - ppublish
SO  - Immunology. 1997 Dec;92(4):512-8. doi: 10.1046/j.1365-2567.1997.00385.x.