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 investigated whether cell surface proteoglycan CD44 can mediate adhesion of human CD34+ HPC to immobilized hyaluronan (HA), an abundant glycosaminoglycan of the bone marrow extracellular matrix. Our data show that, although CD34+ cells strongly express CD44, only 13.3% +/- 1.1% spontaneously adheres to HA. Short-term methylcellulose assay showed that HA-adherent 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 adhered to HA. Moreover, we found that CD44-mediated adhesion of CD34+ cells to HA could be enhanced by phorbol 12-myristate 13-acetate (PMA), the function-activating anti-CD44 monoclonal antibody H90, and cytokines such as granulocyte-monocyte colony-stimulating factor, interleukin-3 (IL-3), and stem cell factor. Enhancement through PMA required several hours, was protein-synthesis-dependent, and was associated with an increase of CD44 cell surface expression, whereas stimulation of adhesion by H90 monoclonal antibody and cytokines was very rapid and without 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 adhere to HA via CD44, point out that this adhesive interaction to HA is a process that may also be physiologically regulated by cytokines.
Legras
S
S
Institut National de la Santé et de la Recherche Medicale U268, Hôpital Paul Brousse, Villejuif, France.
Levesque
J P
JP
Charrad
R
R
Morimoto
K
K
Le Bousse
C
C
Clay
D
D
Jasmin
C
C
Smadja-Joffe
F
F
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D006820:Hyaluronic Acid / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000096:biosynthesis; D019089:Stem Cell Factor / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D007377:Interleukin-3; D008562:Membrane Glycoproteins; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006820:Hyaluronic Acid; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D013755:Tetradecanoylphorbol Acetate