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Blood, 1 June 2002, Vol. 99, No. 11, pp. 3955-3961
HEMATOPOIESIS
CD44 variant-specific antibodies trigger
hemopoiesis by selective release of cytokines from bone marrow
macrophages
Sophia Khaldoyanidi,
Svetlana Karakhanova,
Jonathan Sleeman,
Peter Herrlich, and
Helmut Ponta
From Forschungszentrum Karlsruhe, Institute of
Toxicology and Genetics, and University of Karlsruhe, Institute of
Genetics, Karlsruhe, Germany.
Hemopoiesis is regulated by the complex interplay between the bone
marrow microenvironment and hemopoietic stem cells and progenitors. The
local production of cytokines plays a critical role in this process.
Using long-term bone marrow cultures, we show here that monoclonal
antibodies directed against the CD44 v4 and CD44 v6 epitopes stimulate
myelopoiesis (CD44 v4 and CD44 v6) and lymphopoiesis (CD44 v6). In the
bone marrow cell population, CD44 v4 and CD44 v6 epitopes are found
virtually exclusively on double-positive bone marrow macrophages. The
anti-CD44 v4 and v6 antibodies act on bone marrow macrophages to
stimulate granulocyte-macrophage colony-stimulating factor (GM-CSF)
production (v4 and v6) and interleukin-6 (IL-6) production (v6). This
profile of cytokine production explains the differential stimulation of
hemopoiesis by the 2 antibodies. We suggest that the antibodies mimic
ligand(s) that stimulate GM-CSF or IL-6 production by bone
marrow-derived macrophages by binding to CD44 family members that bear
CD44 v4 and CD44 v6 epitopes on these cells.
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