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CD44-mediated adhesiveness of human hematopoietic progenitors to hyaluronan
is modulated by cytokines
S Legras, JP Levesque, R Charrad, K Morimoto, C Le Bousse, D Clay, C Jasmin and F Smadja-Joffe
Institut National de la Sante et de la Recherche Medicale U268, Hopital
Paul Brousse, Villejuif, France.
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.
Volume 89,
Issue 6,
pp. 1905-1914,
03/15/1997
Copyright © 1997 by The American Society of Hematology

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