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Modulation of macrophage and B cell function by glycosaminoglycans
Author(s) -
Wrenshall Lucile E.,
Stevens R. Brian,
Cerra Frank B.,
Platt Jeffrey L.
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.66.3.391
Subject(s) - glycosaminoglycan , microbiology and biotechnology , dermatan sulfate , heparan sulfate , immune system , biology , cytotoxic t cell , chondroitin sulfate , macrophage , antigen , immunology , biochemistry , in vitro
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 β, and prostaglandin E 2 (PGE 2 ), and (in macrophages) induced cytotoxic capability. Heparin induced IL‐12 and interferon‐γ production but did not promote the release of other cytokines. Chondroitin sulfate and dermatan sulfate, although not stimulating the production of cytokines or of PGE 2 , 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. J. Leukoc. Biol. 66: 391–400; 1999.