PSGL-1-mediated adhesion of human hematopoietic progenitors to P-selectin results in suppression of hematopoiesis.
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.
Lévesque
J P
JP
Division of Haematology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, SA, Australia.
Zannettino
A C
AC
Pudney
M
M
Niutta
S
S
Haylock
D N
DN
Snapp
K R
KR
Kansas
G S
GS
Berndt
M C
MC
Simmons
P J
PJ
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D016466:CHO Cells; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D006224:Cricetinae; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009244:NAD+ Nucleosidase; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D019089:Stem Cell Factor / Q000378:metabolism / Q000494:pharmacology
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D007377:Interleukin-3; D015850:Interleukin-6; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1