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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2587-2595
HEMATOPOIESIS
Stromal cell-derived factor 1 increases
polyploidization of megakaryocytes generated by human hematopoietic
progenitor cells
Raffaella Guerriero,
Gianfranco Mattia,
Ugo Testa,
Cristiana Chelucci,
Giampiero Macioce,
Ida Casella,
Paola Samoggia,
Cesare Peschle, and
Hamisa Jane Hassan
From the Department of Clinical Biochemistry and the
Department of Hematology-Oncology, Istituto Superiore di Sanità,
Rome, Italy; and Thomas Jefferson University, Philadelphia, PA.
The alpha chemokine receptor CXCR4 has been shown to be expressed
on human hematopoietic progenitor cells and during the
megakaryocytic differentiation pathway. Stromal cell-derived factor 1 (SDF-1) is the ligand for CXCR4. In this study, the role of SDF-1 in megakaryocytopoiesis was investigated. CD34+ progenitors
purified from peripheral blood were grown in serum-free liquid
suspension culture supplemented with thrombopoietin to obtain a
virtually pure megakaryocytic progeny. In this condition, the addition
of SDF-1 gives rise to megakaryocytes (MKs) showing an increased DNA
content and a rise of lobated nuclei, as compared with untreated cells:
at day 5, approximately 20% of the cells already showed the presence
of more than one nuclear lobe versus fewer than 5% in the control
cells; at day 12, approximately 85% of the cells were of large size
and markedly polyploid, whereas approximately 60% of the control cells
were polyploid, showed fewer lobes, and were a smaller size. This
effect was dose-dependent and did not affect the megakaryocytic
proliferation. Experiments with the mitogen-activated protein kinase
(MAPK) inhibitor PD98059 suggested a role for MAPK pathway on
SDF-1-induced endomitosis. Furthermore, SDF-1 induced a
significant increase in the number of proplatelet-bearing MKs and
promoted the migration of megakaryocytic cells. Treatment with SDF-1
caused reduction in CXCR4 abundance on the plasma membrane, seemingly
owing to receptor internalization. Furthermore, the presence of
SDF-1 did not affect the expression of megakaryocytic markers,
indicating that differentiation and polyploidization are independently
regulated events.
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