DIFFERENTIAL-EFFECTS OF CHONDROITIN SULFATE-A AND SULFATE-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 mo nonuclear leukocytes and released as a consequence of extracellular ma trix degradation. Chondroitin 4-sulfate proteoglycans constitute the p redominant 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, Wherea s CSA activates monocytes (to secrete monokines), CSB activates B-cell s (to proliferate). In contrast, the chondroitin a-sulfate CSC and hep arin do not exert these functional effects. We further show that CD44 monoclonal antibodies block CSB-induced B-cell proliferation. These fi ndings point to glycosaminoglycans, and specifically chondroitin 4-sul fates, as a novel class of immunological mediators at inflammatory sit es. Furthermore, the data link CD44 to B-cell activation, paralleling the established roles of CD44 in T-cell and monocyte activation. (C) 1 998 by The American Society of Hematology.