Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
The role of HIV-related chemokine receptors and chemokines in human erythropoiesis in vitro.
Stem Cells. 2000;18(2):128-38. Unique Identifier : AIDSLINE MED/20209089 Majka M; Ratajczak J; Lee B; Honczarenko M; Douglas R; Kowalska MA; Silberstein L; Gewirtz AM; Ratajczak MZ; Department of Pathology & Laboratory Medicine, Children's; Hospital of Philadelphia, PA 19104, USA.
Abstract:
In order to better define the role of HIV-related chemokines in human erythropoiesis we studied: A) the expression of chemokine receptors, both on human CD34(+) cells which include erythroid progenitors and on more mature erythroid cells; B) the functionality of these receptors by calcium flux, chemotaxis assay and phosphorylation of mitogen-activated protein kinases (MAPK) p42/44 (ERK1/ERK2) and AKT, and finally C) the influence of chemokines on BFU-E formation. We found that HIV-related chemokine receptor CXCR4, but not CCR5, is detectable on human CD34(+) BFU-E cells. CXCR4 surface expression decreased during erythroid maturation, although CXCR4 mRNA was still present in cells isolated from differentiated erythroid colonies. SDF-1, a CXCR4 ligand, induced calcium flux and phosphorylation of MAPK (p42/44) and AKT in CD34(+)KIT(+) bone marrow mononuclear cells which contain BFU-E, as well as chemotactic activity of both human CD34(+) BFU-E progenitors and erythroid cells isolated from day 2-6 BFU-E colonies. Responsiveness to SDF-1 decreased when the cells differentiated to the point of surface expression of the erythroid-specific marker Glycophorin-A. In contrast, the CCR5 ligands (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, and RANTES) did not activate calcium flux, MAPK and AKT phosphorylation or chemotaxis of CD34(+)KIT(+) cells or cells isolated from the BFU-E colonies. Interestingly, none of the chemokines tested in this study had any effect on BFU-E colony formation. In conclusion, only CXCR4 is functional, and its specific ligand SDF-1 may therefore play an important role in the homing and/or retention of early erythroid precursors in the bone marrow environment.
Keywords: JOURNAL ARTICLE p42 MAP Kinase/METABOLISM Antigens, CD34 Calcium/METABOLISM Cell Division Cells, Cultured Chemokines/*PHYSIOLOGY Chemotaxis Culture Media, Serum-Free Erythroid Progenitor Cells/CYTOLOGY/METABOLISM Erythropoiesis/*PHYSIOLOGY Gene Expression Hematopoietic Stem Cells/CYTOLOGY/METABOLISM Human HIV/*METABOLISM Ligands Mitogen-Activated Protein Kinases/METABOLISM Phosphorylation Receptors, Chemokine/GENETICS/*PHYSIOLOGY Support, U.S. Gov't, P.H.S.
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Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
