Suppressive effects of TNF-alpha, TGF-beta 1, and chemokines on megakaryocytic colony formation in CD34(+) cells derived from umbilical cord blood compared with mobilized peripheral blood and bone marrow

Citation
L. Lu et al., Suppressive effects of TNF-alpha, TGF-beta 1, and chemokines on megakaryocytic colony formation in CD34(+) cells derived from umbilical cord blood compared with mobilized peripheral blood and bone marrow, J HEMATH ST, 9(2), 2000, pp. 195-204
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH
ISSN journal
1525-8165 → ACNP
Volume
9
Issue
2
Year of publication
2000
Pages
195 - 204
Database
ISI
SICI code
1525-8165(200004)9:2<195:SEOTT1>2.0.ZU;2-8
Abstract
CD34(+) cells from human umbilical cord blood (CB) were isolated and invest igated for megakaryocytic (MK) colony formation in response to recombinant human (rh) stimulatory and suppressive cytokines and compared with their co unterparts in normal BM and G-CSF-mobilized peripheral blood (mPBL). First, we observed that IL-11 by itself at any dosage had no stimulator activity on MK colony formation derived from CD34(+) cells in CB, mPBL, and BM. IL-3 , steel factor (SLF), or thrombopoietin (Tpo) alone stimulated numbers of c olony-forming unit-megakaryocyte (CFU-MK) in a dose-dependent fashion. Maxi mum growth of MK progenitor cells was noted in the presence of a combinatio n of cytokines: IL-11, IL-3, SLF, and Tpo. The frequency of CFU-MK in CB an d mPBL was significantly greater than that in BM, and the size of colonies in CB and mPBL was significantly greater than that in BM, and the size of c olonies was larger as well. In addition, an increased number of big mixed c olonies containing MK were observed in CB and mPBL. In the presence of IL-1 1, IL-3, SLF, and Tpo, CFU-MK derived from CB, mPBL, and BM was suppressed by tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-b eta 1 (TGF-beta 1). CFU-MK derived from normal BM was inhibited by some che mokines evaluated, whereas CFU-MK derived from CB was suppressed only by pl atelet factor-4 (PF-4), IFN-inducible protein-ill (IP-10), Exodus-l, Exodus -2, and Exodus-3, but to a lesser degree. In CB, unlike granulocyte-macroph age (CFU-GM), erythroid (BFU-E), high-proliferative potential (HPP-CFC), or multipotential (CFU-GEMM) progenitors, at least a subpopulation of MK prog enitors are in S-phase. Therefore, CB MK progenitors respond to the suppres sive effects of some members of the chemokine family. Similar results were noted for burst-forming unit-MK (BFU-MK). Our results indicate that CB and mPBL are rich sources of MK progenitors and that MK progenitors in CB are r esponsive to the suppressive effects of TNF-alpha and TGF-beta 1 and some m embers of the chemokine family.