Abstract
CD45 antigens are protein tyrosine phosphatases. A possible link was evaluated between expression of CD45 antigens on human myeloid progenitor cells (MPC) (colony-forming unit-granulocyte/macrophage [CFU-GM], burst-forming unit-erythroid [BFU-E], and colony-forming unit-granulocyte/erythroid/macrophage/megakaryocyte [CFU-GEMM]) and regulation of MPC by colony-stimulating factors (CSF) (interleukin 3 [IL-3], GM-CSF, G-CSF, M-CSF, and erythropoietin [Epo]), a GM-CSF/IL-3 fusion protein, and mast cell growth factor (MGF; a c-kit ligand). Treatment of cells with antisense oligodeoxynucleotides (oligos) to exons 1 and 2, but not 4, 5, or 6, of the CD45 gene, or with monoclonal anti-CD45, significantly decreased CFU-GM colony formation stimulated with GM-CSF, IL-3, fusion protein, and GM-CSF + MGF, but not with G-CSF or M-CSF. It also decreased GM-CSF, IL-3, fusion protein, and MGF-enhanced Epo-dependent BFU-E and CFU-GEMM colony formation, but had little or no effect on BFU-E or CFU-GEMM colony formation stimulated by Epo alone. Similar results were obtained with unseparated or purified (greater than or equal to one of two cells being a MPC) bone marrow cells. Sorted populations of CD343+ HLA-DR+ marrow cells composed of 90% MPC were used to demonstrate capping of CD45 after crosslinking protocols. Also, a decreased percent of CD45+ cells and CD45 antigen density was noted after treatment of column-separated CD34+ cells with antisense oligos to exon 1 of the CD45 gene. These results demonstrate that CD45 cell surface antigens are linked to stimulation of early human MPC by IL-3, GM-CSF, a GM-CSF/IL-3 fusion protein, and MGF.
MeSH Terms
Animals
Antibodies, Monoclonal
Antigens, CD/genetics,physiology
Antisense Elements (Genetics)
Base Sequence
Bone Marrow Cells
Cell Differentiation
Cells, Cultured
Exons
Granulocyte-Macrophage Colony-Stimulating Factor/physiology
Hematopoietic Cell Growth Factors/physiology
Hematopoietic Stem Cells/cytology
Histocompatibility Antigens/genetics,physiology
Humans
Interleukin-3/physiology
Leukocyte Common Antigens
Leukocytes/cytology
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Oligonucleotides
Recombinant Fusion Proteins/pharmacology
Stem Cell Factor
Chemicals
Antibodies, Monoclonal
Antigens, CD
Antisense Elements (Genetics)
Hematopoietic Cell Growth Factors
Histocompatibility Antigens
Interleukin-3
Oligonucleotides
Recombinant Fusion Proteins
Stem Cell Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Leukocyte Common Antigens
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Broxmeyer H E
Department of Medicine Hematology/Oncology, Indiana University School of Medicine, Indianapolis 46202.
Lu L
Hangoc G
Cooper S
Hendrie P C
Ledbetter J A
Xiao M
Williams D E
Shen F W
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