CD44-MEDIATED ADHESIVENESS OF HUMAN HEMATOPOIETIC PROGENITORS TO HYALURONAN IS MODULATED BY CYTOKINES

Adhesive interactions between CD34(+) hematopoietic progenitor cells ( HPC) and bone marrow stroma are crucial for normal hematopoiesis, yet their molecular bases are still poorly elucidated. We have investigate d whether cell surface proteoglycan CD44 can mediate adhesion of human CD34(+) HPC to immobilized hyaluronan (HA), an abundant glycosaminogl ycan of the bone marrow extracellular matrix, Our data show that, alth ough CD34(+) cells strongly express CD44, only 13.3+/-1.1% spontaneous ly adheres to HA. Short-term methylcellulose assay showed that HA-adhe rent CD34(+) cells comprised granulo-monocytic and erythroid committed progenitors (19.6%+/-2.5% and 7.3%+/-1.0% of the input, respectively) . More primitive progenitors, such as pre-colony-forming units, also a dhered to HA. Moreover, we found that CD44-mediated adhesion of CD34() cells to HA could be enhanced by phorbol 12-myristate It-acetate (PM A), the function-activating anti-CD44 monoclonal antibody H90, and cyt okines such as granulocyte-monocyte colony-stimulating factor, interle ukin-3 (IL-3), and stem cell factor. Enhancement through PMA required several hours, was protein-synthesis-dependent, and was associated wit h an increase of CD44 cell surface expression, whereas stimulation of adhesion by H90 monoclonal antibody and cytokines was very rapid and w ithout alteration of CD44 expression. H90-induced activation occurred at 4 degrees C and lasted for at least 2 hours, whereas activation by cytokines required incubation at 37 degrees C and was transient. These data, which show for the first time that CD34(+) HPC can directly adh ere to HA via CD44, point out that this adhesive interaction to HA is a process that may also be physiologically regulated by cytokines. (C) 1997 by The American Society of Hematology.