CD44 AND HYALURONAN-BINDING BY HUMAN MYELOID CELLS

The CD44 cell surface molecule has been shown to be the principal cell surface receptor for hyaluronan (or hyaluronic acid), a glycosaminogl ycan component of marrow extracellular matrix. However, its affinity f or hyaluronan is not constitutive, since it depends on the cell type, the stage of differentiation and on activation by external stimuli inc luding certain anti-CD44 antibodies and phorbol esters. Except for a f ew lymphoid cell lines, hematopoietic cells do not spontaneously bind hyaluronan and initial studies reported that, contrary to lymphocytes, myeloid cells could not be activated to bind hyaluronan. Because CD44 plays an important role in the initial phases of hematopoiesis, as sh own by experiments using blocking anti-CD44 monoclonal antibodies, its capacity to mediate adhesion of primitive myeloid cells has been inve stigated. It was found that CD44 could mediate spontaneous adhesion to hyaluronan of immature myeloid cell lines KG1, KG1a, and TF1, which s erve as a model for hematopoietic progenitors. However, despite expres sing high amounts of CD44, no more than 15% of bone marrow progenitors could adhere to hyaluronan. Recent experiments have shown that a very important feature of CD44 is its capacity to be rapidly activated by certain antibodies and cytokines (GM-CSF and KL) from a low affinity t o a high affinity state for hyaluronan. These data shed light on strik ing similarities in the functional regulation of CD44 and of the two i ntegrin receptors VLA-4 (a4b1), and VLA-5 (a5b1), which are also expre ssed on hematopoietic progenitors. The relevance of these data to the regulation of normal hematopoiesis and mobilization of CD34+ progenito rs in the view of cell grafting is analyzed. In addition, we show that in idiopathic myelofibrosis, the amount of hyaluronan is markedly inc reased in the extracellular matrix from the myeloproliferative spleen. Considering that the production of cytokines is enhanced in this dise ase, we discuss whether CD44-hyaluronan interaction may have a role in the pathophysiology of this myeloproliferative syndrome.