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Departments of Microbiology/Immunology and Medicine and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, and Walther Cancer Institute, Indianapolis, IN 46208; and Departments of
Molecular Virology and Host Defense, Collegeville, PA 19426 and
Molecular Immunology, SmithKline Beecham Pharmaceuticals and King of Prussia, PA 19406
Chemoattractants are potential factors influencing cell migration.
Stromal cell-derived factor-1, a CXC chemokine, is the only chemokine
reported to have chemotactic activity for hemopoietic progenitor cells
(HPC). We report in this work another chemokine of the CC subfamily,
which is chemotactic for HPC. Macrophage-inflammatory protein
(MIP)-3ß/EBI1-ligand chemokine/CKß-11 attracted bone marrow and
cord blood CD34+ cells. In contrast to stromal cell-derived
factor-1, which attracts multiple types of HPC, MIP-3ß attracted
mainly CFU granulocyte macrophage, but not other HPC such as
burst-forming unit erythrocyte or CFU granulocyte, erythrocyte,
macrophage, and megakaryocyte. Chemoattracted CD34+ cells
formed CFU granulocyte macrophage-like colonies, which were
morphologically determined as large macrophages. These progenitors were
selectively responsive to stimulation by macrophage CSF, demonstrating
that MIP-3ß attracts macrophage progenitors. Expression of CCR7, the
receptor for MIP-3ß, was detected at a mRNA level in the attracted
CD34+ cells as well as input CD34+HPC.
Expression of MIP-3ß mRNA was not constitutive, but was inducible in
bone marrow stromal cells by inflammatory agents such as bacterial LPS,
IFN-
, and TNF-
. Taken together, our findings suggest that
MIP-3ß is expressed in the bone marrow environment after induction
with certain inflammatory cytokines and LPS, and may play a role in
trafficking of macrophage progenitors in and out of the bone marrow in
inflammatory conditions.
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