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Expression and factor-dependent modulation of the interleukin-3 receptor subunits on human hematopoietic cells
- Source :
- Europe PubMed Central
- Publication Year :
- 1993
- Publisher :
- American Society of Hematology, 1993.
-
Abstract
- Interleukin-3 (IL-3) regulates growth and differentiation of multipotential as well as lineage-committed progenitor cells. The human IL-3 receptor (IL-3R) consists of the alpha and common beta (beta c) subunits. The alpha subunit (IL-3R alpha) is specific for IL-3 and binds IL-3 with low affinity. In contrast, the beta c subunit does not bind any cytokine by itself, but forms a high-affinity receptor with IL- 3R alpha. As the same beta c subunit also forms high-affinity receptors for IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) with the respective cytokine-specific alpha subunit, the expression of the alpha subunits is responsible for specificity of cytokines. To examine the expression of IL-3R alpha, we have developed a monoclonal antibody (MoAb), N3A. N3A specifically bound to cells expressing IL-3R alpha and immunoprecipitated a 75 Kd glycoprotein, which became 43 Kd on N-glycosidase digestion. N3A and an anti-beta c antibody, CRS1, were used in double color fluorescence-activated cell sorter (FACS) staining with several lineage markers to see the IL-3R expression pattern in peripheral blood (PB), cord blood (CB), and bone marrow (BM) cells. Both IL-3R subunits were expressed on myeloid cell lineages (CD13+, CD14+, CD15Lo, or CD33+). To further study the IL-3R expression on hematopoietic progenitor cells, the CD34+ populations were isolated from both BM and CB cells. Those populations showed positive staining profiles with the N3A MoAb and were weakly stained with the CRS1 MoAb. Furthermore, anti c-kit antibody staining of the CD34+ fraction from CB, but not from BM, showed two intensities and the IL-3R alpha expression seemed to be higher in a fraction of low c-kit expression. Because IL-1, IL-6, G-CSF, stem cell factor (SCF), interferon (IFN)- gamma, and tumor necrosis factor (TNF)-alpha are known to enhance IL-3- dependent colony formation, we have examined whether this enhancement could be correlated with upregulation of the IL-3R expression. Incubation of CD34+ cells with TNF-alpha for 2 days significantly increased the level of beta c and G-CSF increased the number of cells with high level expression of alpha, while other factors did not affect the IL-3R expression. Thus, different cytokines appear to have different mechanisms for enhancement of IL-3-dependent proliferation.
- Subjects :
- Immunology
Interleukin 5 receptor alpha subunit
Alpha (ethology)
Antigens, CD34
Bone Marrow Cells
Stem cell factor
In Vitro Techniques
Biology
Biochemistry
Cell Line
Immunophenotyping
Interleukin 10 receptor, alpha subunit
Antigens, CD
Cell surface receptor
Humans
Progenitor cell
Interleukin 3
G alpha subunit
Antibodies, Monoclonal
Cell Biology
Hematology
Fetal Blood
Flow Cytometry
Hematopoietic Stem Cells
Precipitin Tests
Molecular biology
Receptors, Interleukin-3
Cytokines
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....d92902e702ec719ae6277f726cc827bd