Differential effects of chondroitin sulfates A and B on monocyte and B-cell activation: evidence for B-cell activation via a CD44-dependent pathway.
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.
Rachmilewitz
J
J
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Tykocinski
M L
ML
D001402:B-Lymphocytes / Q000276:immunology*; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D003871:Dermatan Sulfate / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
D018960:Hyaluronan Receptors; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates