Modulation of macrophage and B cell function by glycosaminoglycans.
There is increasing evidence that the behavior of antigen-presenting cells may be regulated, in part, by the surrounding microenvironment. Components of the microenvironment of solid tissues that might influence antigen-presenting cell functions include glycosaminoglycans. We previously showed that heparan sulfate glycosaminoglycans activate macrophages, leading to profound alterations in T cell responses. Here we demonstrate the functional changes that occur in murine antigen-presenting cells induced by heparan sulfate and other glycosaminoglycans, and postulate how these functional changes influence the nature of local immune responses. Heparan sulfate triggered up-regulation of ICAM-1 and I-A, caused the release by antigen-presenting cells of interleukin (IL)-1, IL-6, tumor necrosis factor, IL-12, transforming growth factor beta, and prostaglandin E2 (PGE2), and (in macrophages) induced cytotoxic capability. Heparin induced IL-12 and interferon-gamma production but did not promote the release of other cytokines. Chondroitin sulfate and dermatan sulfate, although not stimulating the production of cytokines or of PGE2, elicited the production by macrophages of nitric oxide. These findings support a model in which the glycosaminoglycan composition of a given tissue, which may be altered by inflammatory processes, helps to regulate the behavior of antigen-presenting cells, which in turn determines the characteristics of the immune response that ensues.
Wrenshall
L E
LE
Department of Surgery, University of Minnesota, Minneapolis, USA. lew@u.washington.edu
Stevens
R B
RB
Cerra
F B
FB
Platt
J L
JL
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003871:Dermatan Sulfate / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D015232:Dinoprostone; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha