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Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 940-949
Hyaluronate-Enhanced Hematopoiesis: Two Different Receptors Trigger the
Release of Interleukin-1 and Interleukin-6 From Bone Marrow
Macrophages
Sophia Khaldoyanidi,
Jürgen Moll,
Svetlana Karakhanova,
Peter Herrlich, and
Helmut Ponta
From Forschungszentrum Karlsruhe, Institute of Genetics,
Karlsruhe, Germany.
The glycosaminoglycan hyaluronate (HA) is part of the extracellular
environment in bone marrow. We show here that HA activates signal
transduction cascades important for hemopoiesis. In myeloid and
lymphoid long-term bone marrow cultures (LTBMC), treatment with
hyaluronidase (HA'ase) results in reduced production of both progenitor and mature cells. Exogeneous HA added to LTBMC had the
opposite effect: it enhanced hematopoiesis. The effect of HA is mediated through two different HA receptors on bone marrow macrophage-like cells, one of which is CD44 while the other is unknown.
HA induces bone marrow macrophages to secrete IL-1 (CD44-dependent) and IL-6 (CD44-independent). The two receptors address different signal
transduction pathways: CD44 links to a pathway activating p38 protein
kinase while the other yet unknown receptor induces Erk activity. There
was no difference of the effect of HA and HA'ase on hematopoiesis in
LTBMC and on cytokine production by macrophages in CD44-deficient mice
compared with wild-type mice, indicating that the CD44 hyaluronate
receptor and its signal transduction can be compensated for. Our data
suggest a regulatory role for the extracellular matrix component HA in
hematopoiesis and show the induction of signal transduction by HA receptors.
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