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-prese nting cell functions include glycosaminoglycans, were previously showed tha t heparan sulfate glycosaminoglycans activate macrophages, leading to profo und alterations in T cell responses. Here we demonstrate the functional cha nges that occur ia murine antigen-presenting cells induced by heparan sulfa te 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 c ells of interleukin (IL)-1, IL-6, tumor necrosis factor, IL-12, transformin g growth factor beta, and prostaglandin E-2 (PGE(2)), and tin macrophages) induced cytotoxic capability. Heparin induced IL-12 and interferon-gamma pr oduction but did not promote the release of other cytokines, Chondroitin su lfate and dermatan sulfate, although not stimulating the production of cyto kines 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 determine s the characteristics of the immune response that ensues.