Abstract
Cellular interactions are critical for the regulation of hematopoiesis. The sialomucin PSGL-1/CD162 mediates the attachment of mature leukocytes to P-selectin. We now show that PSGL-1 also functions as the sole receptor for P-selectin on primitive human CD34+ hematopoietic progenitor cells (HPC). More importantly, ligation of PSGL-1 by immobilized or soluble ligand or anti-PSGL-1 antibody results in a profound suppression of HPC proliferation stimulated by potent combinations of early acting hematopoietic growth factors. These data demonstrate an unanticipated but extremely marked growth-inhibitory effect of P-selectin on hematopoiesis and provide direct evidence that PSGL-1, in addition to its well-documented role as an adhesion molecule on mature leukocytes, is a potent negative regulator of human hematopoietic progenitors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ADP-ribosyl Cyclase
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ADP-ribosyl Cyclase 1
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Animals
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Antigens, CD*
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Antigens, CD34
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Antigens, Differentiation
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Apoptosis
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / physiology
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CHO Cells
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Cell Adhesion*
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Cell Division
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Cells, Cultured
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Cricetinae
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Granulocyte Colony-Stimulating Factor / metabolism
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Granulocyte Colony-Stimulating Factor / pharmacology
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Hematopoiesis / physiology*
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Hematopoietic Stem Cells / metabolism
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Hematopoietic Stem Cells / physiology*
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Humans
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Interleukin-3 / metabolism
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Interleukin-3 / pharmacology
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Interleukin-6 / metabolism
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Interleukin-6 / pharmacology
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Ligands
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Membrane Glycoproteins / metabolism*
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NAD+ Nucleosidase
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P-Selectin / genetics
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P-Selectin / metabolism*
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Solubility
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Stem Cell Factor / metabolism
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Stem Cell Factor / pharmacology
Substances
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Antigens, CD
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Antigens, CD34
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Antigens, Differentiation
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Interleukin-3
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Interleukin-6
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Ligands
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Membrane Glycoproteins
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P-Selectin
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P-selectin ligand protein
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Stem Cell Factor
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Granulocyte Colony-Stimulating Factor
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ADP-ribosyl Cyclase
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CD38 protein, human
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NAD+ Nucleosidase
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ADP-ribosyl Cyclase 1