Differential Effects of Chondroitin Sulfates A and B on Monocyte and B-Cell Activation: Evidence for B-Cell Activation Via a CD44-Dependent Pathway

Abstract

At inflammatory sites, proteoglycans are both secreted by activated mononuclear leukocytes and released as a consequence of extracellular matrix degradation. Chondroitin 4-sulfate proteoglycans constitute the predominant ones produced by activated human monocytes/macrophages. In this study, we show that two chondroitin 4-sulfate forms, CSA and CSB, can activate distinct peripheral blood mononuclear cell types. Whereas CSA activates monocytes (to secrete monokines), CSB activates B-cells (to proliferate). In contrast, the chondroitin 6-sulfate CSC and heparin do not exert these functional effects. We further show that CD44 monoclonal antibodies block CSB-induced B-cell proliferation. These findings point to glycosaminoglycans, and specifically chondroitin 4-sulfates, as a novel class of immunological mediators at inflammatory sites. Furthermore, the data link CD44 to B-cell activation, paralleling the established roles of CD44 in T-cell and monocyte activation.