The α-Chemokine Receptor CXCR4 Is Expressed on the Megakaryocytic Lineage From Progenitor to Platelets and Modulates Migration and Adhesion

Abstract

CXCR4 is the receptor for the α-chemokine stromal cell-derived factor 1 (SDF-1) and has been shown to be expressed on a diversity of leukocytes. In this report, the expression of the CXCR4 receptor in cells of megakaryocytic lineage and the role of SDF-1 in megakaryocytopoiesis were investigated. Using flow cytometry in combination with reverse transcriptase-polymerase chain reaction (RT-PCR), we observed that bone marrow CD34+, CD61+ cells, blood platelets, and megakaryocytic leukemia cell lines all expressed the CXCR4 receptor. To examine the expression of the CXCR4 receptor on megakaryocyte progenitors (colony-forming units-megakaryocyte [CFU-Meg]), CXCR4-positive and -negative CD34+ populations were separated from bone marrow and cultured in a plasma clot culture system. A subpopulation of the CFU-Meg was found in the CXCR4-positive fraction. The functional significance of CXCR4 expression on cells of the megakaryocytic lineage was examined by studying the effects of SDF-1α on migration and proliferation of megakaryocyte progenitor cells in vitro. We found that SDF-1α potently induced megakaryocyte progenitor migration and significantly enhanced adhesion of mature marrow megakaryocytes to endothelium. No marked effects of SDF-1α alone or in combination with thrombopoietin and stem cell factor/kit ligand on megakaryocyte production in vitro were noted. These results demonstrate for the first time that the CXCR4 α-chemokine receptor is expressed on cells of the megakaryocytic lineage from progenitors to platelets and that its ligand SDF-1α may modulate several aspects of megakaryocytopoiesis. © 1998 by The American Society of Hematology.

Productive Infection of CD34+-Cell-Derived Megakaryocytes by X4 and R5 HIV-1 Isolates

“…Most importantly, these CD34ϩcell-derived megakaryocytes have been reported to be morphologically identical to bone marrow megakaryocytes and to produce platelets in vitro that are indistinguishable from normal platelets (Choi et al, 1995a,b;Cramer et al, 1997). We showed, in agreement with published reports, that CD41ϩ megakaryocytes express surface CD4, CXCR4, and CCR5 (Gewirtz et al, 1992;Kouri et al, 1993;Zauli et al, 1995;Basch et al, 1996;Wang et al, 1998;Kowalska et al, 1999;Lee et al, 1999;Riviere et al, 1999) and may be susceptible to infection by both X4 and R5 HIV-1 strains. In addition, we report for the first time, the presence of the CCR3 chemokine receptor on CD34ϩ-cell-derived megakaryocytes.…”

Platelet chemokines and their receptors: what is their relevance to platelet storage and transfusion practice?

“…CXCR4 is mainly expressed on neutrophils, monocytes, dendritic cells (DC), T and B lymphocytes, thymocytes and CD34+ cells from blood and bone marrow. Thus, it is also expressed on cells of the megakaryocytic lineage from progenitors to platelets (Wang et al ., 1998; Kowalska et al ., 1999; Riviere et al ., 1999; Clemetson et al ., 2000). It was the first chemokine receptor shown to be an human immunodeficiency virus‐1 (HIV‐1) co‐receptor.…”

Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral-blood mononuclear cells in a canine transplantation model

“…Its receptor, CXCR4, is expressed on many different types of hematopoietic cells including megakaryocytes and CD34 ϩ cells. [23][24][25] The bicyclam AMD3100 is a potent, selective, and reversible antagonist of the CXCR4 chemokine receptor and disrupts the binding of CXCR4 to SDF-1, thereby mobilizing hematopoietic cells into the blood. 26 Studies involving animals and humans have shown that AMD3100 treatment resulted in mobilization of hematopoietic progenitor cells [27][28][29][30][31] and that combining AMD3100 with G-CSF had additive effects.…”