CD45 cell surface antigens are linked to stimulation of early human myeloid progenitor cells by interleukin 3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), a GM-CSF/IL-3 fusion protein, and mast cell growth factor (a c-kit ligand).
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.
Broxmeyer
H E
HE
Department of Medicine Hematology/Oncology, Indiana University School of Medicine, Indianapolis 46202.
Lu
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L
Hangoc
G
G
Cooper
S
S
Hendrie
P C
PC
Ledbetter
J A
JA
Xiao
M
M
Williams
D E
DE
Shen
F W
FW
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D005091:Exons; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006649:Histocompatibility Antigens / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology*; D017493:Leukocyte Common Antigens; D007962:Leukocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D019089:Stem Cell Factor
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016375:Antisense Elements (Genetics); D016298:Hematopoietic Cell Growth Factors; D006649:Histocompatibility Antigens; D007377:Interleukin-3; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens