Effects of Short-Term Incubation of Hematopoietic Cells with Hematopoietic Growth Factors on CXCR4 Expression and Stromal Cell-Derived Factor-1-Mediated Transendothelial Migration.
- Author:
Deog Yeon JO
1
;
Jin Hee HWANG
;
Seung Keun KWAK
;
Hyun Young SHIN
;
Sung Eun KIM
;
Hwan Jung YUN
;
Chu Myong SEONG
;
Sam Yong KIM
Author Information
1. Department of Internal Medicine, College of Medicine, Chungnam National University, Taejon, Korea. deogyeon@cuvic.cnu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Hematopoietic cells;
CXCR4;
SDF-1;
Adhesion molecules;
Bone marrow homing;
Hematopoietic growth factors
- MeSH:
Antigens, CD31;
Bone Marrow;
Chemotaxis;
Flow Cytometry;
Granulocyte Colony-Stimulating Factor;
Granulocyte-Macrophage Colony-Stimulating Factor;
Hematopoietic Stem Cells;
Integrin alpha4beta1;
Intercellular Adhesion Molecule-1;
Intercellular Signaling Peptides and Proteins*;
Interleukin-1;
Interleukin-3;
Interleukin-6;
L-Selectin;
Lymphocyte Function-Associated Antigen-1;
Mesenchymal Stromal Cells;
Stem Cell Factor;
Thrombopoietin;
Transendothelial and Transepithelial Migration*;
Up-Regulation
- From:Korean Journal of Hematology
2001;36(4):324-334
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: There has been contradictory reports regarding the homing potential of hematopoietic cells briefly exposed to hematopoietic growth factors in vitro. To get a resolution to this controversy, we investigated the effects of short-term growth factor treatment of hematopoietic cells on the expression of CXCR4 and adhesion molecules, and the chemotaxis in response to stromal cell-derived factor-1 (SDF-1), which is widely accepted to play a critical role in bone marrow (BM) homing of hematopoietic stem cells. METHODS: BM and cord blood(CB) CD34+ cells were incubated with various hematopoietic growth factors including IL-1beta, IL-3, IL-6, G-CSF, GM-CSF, stem cell factor (SCF), flk-2 ligand, and thrombopoietin, alone or in combination for up to 48 hours. Before and after the incubation, the expression of CXCR4 and adhesion molecules of CD34+ cells was analyzed using flow cytometry. SDF-1-mediated transmembrane or transendothelial migration of CD34+ cells, cobblestone area-forming cells (CAFCs), and/or long-term culture-initiating cells (LTC-ICs) was measured using Transwell(TM) system. RESULTS: VLA-4 was moderately up-regulated by the incubation of the cells with IL-3 and SCF, and ICAM-1 was slightly up-regulated by IL-1 and IL-3. The expression of L-selectin, PECAM-1 or LFA-1 was not altered by any growth factors. With the incubation of the cells in the absence of growth factors or SDF-1, CXCR4 expression of CD34+ cells was rapidly increased, reaching a plateau at 24 hours. The spontaneous up-regulation was abrogated with the addition of SDF-1. In agreement with the up-regulation of CXCR4, CD34+ cells incubated for 40 hours showed much enhanced chemotaxis in response to SDF-1 compared to non-incubated cells (24.7 3.5% vs. 7.0 1.6%, P=0.01). Any growth factors examined in this study did not alter the CXCR4 expression of CD34+ cells. Neither did growth factors affect the transendothelial migration of LTC-ICs toward bone marrow stromal cells as well as the SDF-1-induced transmembrane chemotaxis of CD34+ cells and CAFCs. CONCLUSION: Short-term treatment of hemo-topoietic cells with hematopoietic growth factors does not alter the expression of CXCR4 or SDF-1-mediated transendothelial chemotaxis.
