PSGL-1-mediated adhesion of human hematopoietic progenitors to P-selectin results in suppression of hematopoiesis

Immunity. 1999 Sep;11(3):369-78. doi: 10.1016/s1074-7613(00)80112-0.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Animals
  • Antigens, CD*
  • Antigens, CD34
  • Antigens, Differentiation
  • Apoptosis
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / physiology
  • CHO Cells
  • Cell Adhesion*
  • Cell Division
  • Cells, Cultured
  • Cricetinae
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Interleukin-3 / metabolism
  • Interleukin-3 / pharmacology
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology
  • Ligands
  • Membrane Glycoproteins / metabolism*
  • NAD+ Nucleosidase
  • P-Selectin / genetics
  • P-Selectin / metabolism*
  • Solubility
  • Stem Cell Factor / metabolism
  • Stem Cell Factor / pharmacology

Substances

  • Antigens, CD
  • Antigens, CD34
  • Antigens, Differentiation
  • Interleukin-3
  • Interleukin-6
  • Ligands
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Stem Cell Factor
  • Granulocyte Colony-Stimulating Factor
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1