Bone marrow stromal cells produce large amounts of extracellular matrix and cytokines. Amongst them, hyaluronan, a glycosaminoglycan and ligand for the cell surface molecule CD44, and TGF beta 1, a cytokine particularly important in monocyte differentiation. We have studied in vitro the role of hyaluronan and TGF beta 1 in the differentiation process of U937 monocytic progenitor cells. We provide evidence that, in the presence of whole blood-derived serum, the addition of hyaluronan is sufficient to induce the expression of NADPH-oxidase components but not of other rnonocytic markers (CD14, CD11b, and VLA-4). In the presence of plasma-derived serum, besides hyaluronan, the additional presence of TGF beta 1 was required for the expression of all of the components of the NADPH oxidase. We further show that hyaluronan mediates its effect through CD44. We conclude that cell matrix factors act cooperatively with cytokines to induce the expression of the components of the NADPH-oxidase in monocytic progenitor cells. (c) 2006 Elsevier Inc. All rights reserved.