|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 September 2000, Vol. 96, No. 5, pp. 1879-1888
IMMUNOBIOLOGY
Heparin and heparan sulfate bind interleukin-10 and modulate
its activity
Shahram Salek-Ardakani,
John R. Arrand,
David Shaw, and
Mike Mackett
From the CRC Molecular Biology Group, Paterson
Institute for Cancer Research, Christie Hospital NHS Trust, Withington,
Manchester, UK.
Glycosaminoglycans (GAG) are a group of negatively charged
molecules that have been shown to bind and directly regulate the bioactivity of growth factors and cytokines such as basic fibroblast growth factor, transforming growth factor- , IL-7, and
interferon- . The ability of GAG to interact with human IL-10
(hIL-10) and the effect of these interactions on its biologic activity
were analyzed. It was demonstrated by affinity chromatography that
hIL-10 binds strongly to heparin-agarose at physiological pH.
Biosensor-based binding kinetic analysis indicated an equilibrium
dissociation constant, Kd, of 54 nmol/L for
this interaction. Human IL-10 stimulated CD16 and CD64 expression on
the monocyte/macrophage population within peripheral blood mononuclear
cells, with optimal concentrations between 1 and 10 ng/mL. Soluble
heparin, heparan sulfate, chondroitin sulfate, and dermatan sulfate
were shown to inhibit the hIL-10-induced expression of CD16 and CD64
in a concentration-dependent manner. Heparin and heparan sulfate were
most effective with IC50 values of 100 to 500 µg/mL.
Considerably higher concentrations of dermatan sulfate and chondroitin
4-sulfate were required with an IC50 of 2000 to 5000 µg/mL, whereas chondroitin 6-sulfate was essentially inactive. The
antagonistic effect of heparin on hIL-10 activity was shown to be
dependent on N-sulfation, inasmuch as
de-N-sulfated heparin had little or no inhibitory effect on
the IL-10- induced expression of CD16, whereas the effect of
de-O-sulfated heparin was comparable to that of unmodified
heparin. Furthermore, the inhibition of cell-bound proteoglycan
sulfation reduced the hIL-10-mediated expression of CD16 molecules on
monocytes/macrophages. Taken together, these findings support the
hypothesis that soluble and cell-surface GAG and, in particular, their
sulfate groups are important in binding and modulation of hIL-10 activity.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. J. Campbell and C. A. Owen
The Sulfate Groups of Chondroitin Sulfate- and Heparan Sulfate-containing Proteoglycans in Neutrophil Plasma Membranes Are Novel Binding Sites for Human Leukocyte Elastase and Cathepsin G
J. Biol. Chem.,
May 11, 2007;
282(19):
14645 - 14654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Pellequer, Y. Meissner, N. Ubrich, and A. Lamprecht
Epithelial Heparin Delivery via Microspheres Mitigates Experimental Colitis in Mice
J. Pharmacol. Exp. Ther.,
May 1, 2007;
321(2):
726 - 733.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. B. Catterall, A. D. Rowan, S. Sarsfield, J. Saklatvala, R. Wait, and T. E. Cawston
Development of a novel 2D proteomics approach for the identification of proteins secreted by primary chondrocytes after stimulation by IL-1 and oncostatin M
Rheumatology,
September 1, 2006;
45(9):
1101 - 1109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. Smith Jr., J. Novotny, V. S. Carl, and L. D. Comeau
Helicobacter pylori and toll-like receptor agonists induce syndecan-4 expression in an NF-{kappa}B-dependent manner
Glycobiology,
March 1, 2006;
16(3):
221 - 229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Renne, K. Schuh, and W. Muller-Esterl
Local Bradykinin Formation Is Controlled by Glycosaminoglycans
J. Immunol.,
September 1, 2005;
175(5):
3377 - 3385.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. T. Lappegard, M. Fung, G. Bergseth, J. Riesenfeld, and T. E. Mollnes
Artificial surface-induced cytokine synthesis: effect of heparin coating and complement inhibition
Ann. Thorac. Surg.,
July 1, 2004;
78(1):
38 - 44.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Salek-Ardakani, S. A. Lyons, and J. R. Arrand
Epstein-Barr Virus Promotes Human Monocyte Survival and Maturation through a Paracrine Induction of IFN-{alpha}
J. Immunol.,
July 1, 2004;
173(1):
321 - 331.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Strazynski, J. A. Eble, H. Kresse, and E. Schonherr
Interleukin (IL)-6 and IL-10 Induce Decorin mRNA in Endothelial Cells, but Interaction with Fibrillar Collagen Is Essential for Its Translation
J. Biol. Chem.,
May 14, 2004;
279(20):
21266 - 21270.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Nardelli, L. Zaritskaya, M. Semenuk, Y. H. Cho, D. W. LaFleur, D. Shah, S. Ullrich, G. Girolomoni, C. Albanesi, and P. A. Moore
Regulatory Effect of IFN-{kappa}, A Novel Type I IFN, On Cytokine Production by Cells of the Innate Immune System
J. Immunol.,
November 1, 2002;
169(9):
4822 - 4830.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-F. Deux, A. Meddahi-Pelle, A. F. Le Blanche, L. J. Feldman, S. Colliec-Jouault, F. Bree, F. Boudghene, J.-B. Michel, and D. Letourneur
Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model
Arterioscler. Thromb. Vasc. Biol.,
October 1, 2002;
22(10):
1604 - 1609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ali, S. J. Fritchley, B. T. Chaffey, and J. A. Kirby
Contribution of the putative heparan sulfate-binding motif BBXB of RANTES to transendothelial migration
Glycobiology,
September 1, 2002;
12(9):
535 - 543.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Akimov and A. M. Belkin
Cell surface tissue transglutaminase is involved in adhesion and migration of monocytic cells on fibronectin
Blood,
September 1, 2001;
98(5):
1567 - 1576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
