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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1230-1238
CHEMOKINES
CXC chemokine receptor 3 expression on CD34+
hematopoietic progenitors from human cord blood induced by
granulocyte-macrophage colony-stimulating factor: chemotaxis and
adhesion induced by its ligands, interferon  -inducible protein 10 and monokine induced by interferon
Tan Jinquan,
Sha Quan,
Henrik H. Jacobi,
Chen Jing,
Anders Millner,
Bettina Jensen,
Hans O. Madsen,
Lars P. Ryder,
Arne Svejgaard,
Hans-Jørgen Malling,
Per S. Skov, and
Lars K. Poulsen
From the Laboratory of Medical Allergology, Allergy
Unit, and the Laboratory for Tissue Typing, Department of Clinical
Immunology, National University Hospital, Denmark; and the
Department of Immunology, Anhui Medical University, People's
Republic of China.
CXC chemokine receptor 3 (CXCR3), which is known to be expressed
predominately on memory and activated T lymphocytes, is a receptor for
both interferon  (IFN-)-inducible protein 10 (IP-10) and
monokine induced by IFN- (Mig). We report the novel finding that
CXCR3 is also expressed on CD34+ hematopoietic progenitors
from human cord blood stimulated with granulocyte-macrophage
colony-stimulating factor (GM-CSF) but not on freshly isolated
CD34+ progenitors. Freshly isolated CD34+
progenitors expressed low levels of CXCR3 messenger RNA, but this
expression was highly up-regulated by GM-CSF, as indicated by a
real-time quantitative reverse transcriptase-polymerase chain reaction
technique. IP-10 and Mig induced chemotaxis of GM-CSF-stimulated CD34+ progenitors by means of CXCR3, since an anti-CXCR3
monoclonal antibody (mAb) was found to block IP-10-induced and
Mig-induced CD34+ progenitor chemotaxis. These chemotactic
attracted CD34+ progenitors are colony-forming
units granulocyte-macrophage. IP-10 and Mig also induced
GM-CSF-stimulated CD34+ progenitor adhesion and
aggregation by means of CXCR3, a finding confirmed by the observation
that anti-CXCR3 mAb blocked these functions of IP-10 and Mig but not
of chemokine stromal cell-derived factor 1 . IP-10-induced and
Mig-induced up-regulation of integrins (CD49a and CD49b) was found to
play a crucial role in adhesion of GM-CSF-stimulated CD34+
progenitors. Moreover, IP-10 and Mig stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34+
progenitors. These results indicate that CXCR3-IP-10 and CXCR3-Mig receptor-ligand pairs, as well as the effects of GM-CSF on them, may be
especially important in the cytokine/chemokine environment for the
physiologic and pathophysiologic events of differentiation of
CD34+ hematopoietic progenitors into lymphoid and myeloid
stem cells, subsequently immune and inflammatory cells. These processes
include transmigration, relocation, differentiation, and
maturation of CD34+ hematopoietic progenitors.
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