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PMID: 1713254 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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).

The Journal of experimental medicine ·Vol. 174 ·No. 2 ·1991-08-01 ·Pages 447-58

Broxmeyer HE, Lu L, Hangoc G, Cooper S, Hendrie PC, Ledbetter JA, Xiao M, Williams DE, Shen FW

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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36 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1991-08-01
Pages
447-58
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118912
Subset
IM
Grants
NCI NIH HHS · R01 CA-36740 · United States
NCI NIH HHS · R37 CA-36464 · United States
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