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Modulation of macrophage and B cell function by glycosaminoglycans
L E Wrenshall1, R B Stevens, F B Cerra
1Department of Surgery, University of Minnesota, Minneapolis, USA. lew@u.washington.edu
Journal of Leukocyte Biology
|September 25, 1999
Summary
Glycosaminoglycans in the tissue microenvironment regulate antigen-presenting cells. Different glycosaminoglycans induce distinct immune responses, influencing T cell behavior and local immunity.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Antigen-presenting cell (APC) function is influenced by the tissue microenvironment.
- Glycosaminoglycans (GAGs) are key components of the tissue microenvironment.
- Previous work demonstrated heparan sulfate GAGs activate macrophages and alter T cell responses.
Purpose of the Study:
- To investigate functional changes in murine APCs induced by heparan sulfate and other GAGs.
- To understand how these APC functional changes impact local immune responses.
Main Methods:
- Treatment of murine APCs with various GAGs (heparan sulfate, heparin, chondroitin sulfate, dermatan sulfate).
- Analysis of APC surface marker expression (ICAM-1, I-A).
- Measurement of cytokine and mediator release (IL-1, IL-6, TNF, IL-12, TGF-β, PGE2, IFN-γ, nitric oxide).
- Assessment of macrophage cytotoxic capability.
Main Results:
- Heparan sulfate upregulated ICAM-1 and I-A, induced APC release of IL-1, IL-6, TNF, IL-12, TGF-β, and PGE2, and enhanced macrophage cytotoxicity.
- Heparin stimulated IL-12 and IFN-γ production.
- Chondroitin sulfate and dermatan sulfate induced nitric oxide production by macrophages but not cytokine release.
- GAGs differentially modulated APC function and mediator release.
Conclusions:
- GAG composition of the tissue microenvironment regulates APC behavior.
- Altered GAG composition, potentially during inflammation, can modify APC function.
- APC responses to GAGs dictate the characteristics of the ensuing local immune response.