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)

Hal Broxmeyer, Li Lu, Giao Hangoc, Scott Cooper, Paul C. Hendrie, Jeffrey A. Ledbetter, Mang Xiao, Douglas E. Williams, Fung Win Shen

Research output: Contribution to journalArticle

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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, a 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.

Original languageEnglish
Pages (from-to)447-458
Number of pages12
JournalJournal of Experimental Medicine
Volume174
Issue number2
StatePublished - 1991

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Myeloid Progenitor Cells
Stem Cell Factor
Interleukin-3
Surface Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Colony-Stimulating Factors
Granulocyte-Macrophage Progenitor Cells
Proteins
Erythropoietin
CD45 Antigens
Erythroid Precursor Cells
Oligodeoxyribonucleotides
Exons
Protein Tyrosine Phosphatases
Megakaryocytes
HLA-DR Antigens
Granulocytes
Bone Marrow Cells
Genes
Bone Marrow

ASJC Scopus subject areas

  • Immunology

Cite this

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). / Broxmeyer, Hal; Lu, Li; Hangoc, Giao; Cooper, Scott; Hendrie, Paul C.; Ledbetter, Jeffrey A.; Xiao, Mang; Williams, Douglas E.; Shen, Fung Win.

In: Journal of Experimental Medicine, Vol. 174, No. 2, 1991, p. 447-458.

Research output: Contribution to journalArticle

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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, a 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.",
author = "Hal Broxmeyer and Li Lu and Giao Hangoc and Scott Cooper and Hendrie, {Paul C.} and Ledbetter, {Jeffrey A.} and Mang Xiao and Williams, {Douglas E.} and Shen, {Fung Win}",
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T1 - 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)

AU - Broxmeyer, Hal

AU - Lu, Li

AU - Hangoc, Giao

AU - Cooper, Scott

AU - Hendrie, Paul C.

AU - Ledbetter, Jeffrey A.

AU - Xiao, Mang

AU - Williams, Douglas E.

AU - Shen, Fung Win

PY - 1991

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