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

Jean Pierre Lévesque; Andrew C.W. Zannettino; Melanie Pudney; Silvana Niutta; David N. Haylock; Karen R. Snapp; Geoffrey S. Kansas; Michael C. Berndt; Paul J. Simmons

doi:10.1016/S1074-7613(00)80112-0

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

Jean Pierre Lévesque, Andrew C.W. Zannettino, Melanie Pudney, Silvana Niutta, David N. Haylock, Karen R. Snapp, Geoffrey S. Kansas, Michael C. Berndt, Paul J. Simmons^*

^*Corresponding author for this work

Microbiology-Immunology

Research output: Contribution to journal › Article › peer-review

101 Scopus citations

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.

Original language	English (US)
Pages (from-to)	369-378
Number of pages	10
Journal	Immunity
Volume	11
Issue number	3
DOIs	https://doi.org/10.1016/S1074-7613(00)80112-0
State	Published - Sep 1999

Funding

This study was supported by grants to J. P. L. and P. J. S. from the Anti-Cancer Foundation of South Australia (31/97) and the National Health and Medical Research Council of Australia (991522) and to G. S. K. from the American Cancer Society (RPG9609703CSM) and the National Institutes of Health (HL58710). J. P. L. is Chargé de Recherche of the Centre National de la Recherche Scientifique. G. S. K. is an Established Investigator of the American Heart Association. The authors wish to thank Dr. L. Lasky (Genentech, San Francisco, CA) for his kind gift of CD62P-IgG 1 and CD4-IgG 1 fusion proteins and Dr L. B. To for the provision of normal human BM samples.

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

Access to Document

10.1016/S1074-7613(00)80112-0

Cite this

@article{95a410ea6c9c4a0eaae3c1cff1fa43de,

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

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.",

author = "L{\'e}vesque, {Jean Pierre} and Zannettino, {Andrew C.W.} and Melanie Pudney and Silvana Niutta and Haylock, {David N.} and Snapp, {Karen R.} and Kansas, {Geoffrey S.} and Berndt, {Michael C.} and Simmons, {Paul J.}",

note = "Funding Information: This study was supported by grants to J. P. L. and P. J. S. from the Anti-Cancer Foundation of South Australia (31/97) and the National Health and Medical Research Council of Australia (991522) and to G. S. K. from the American Cancer Society (RPG9609703CSM) and the National Institutes of Health (HL58710). J. P. L. is Charg{\'e} de Recherche of the Centre National de la Recherche Scientifique. G. S. K. is an Established Investigator of the American Heart Association. The authors wish to thank Dr. L. Lasky (Genentech, San Francisco, CA) for his kind gift of CD62P-IgG 1 and CD4-IgG 1 fusion proteins and Dr L. B. To for the provision of normal human BM samples.",

year = "1999",

month = sep,

doi = "10.1016/S1074-7613(00)80112-0",

language = "English (US)",

volume = "11",

pages = "369--378",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - PSGL-1-mediated adhesion of human hematopoietic progenitors to P- selectin results in suppression of hematopoiesis

AU - Lévesque, Jean Pierre

AU - Zannettino, Andrew C.W.

AU - Pudney, Melanie

AU - Niutta, Silvana

AU - Haylock, David N.

AU - Snapp, Karen R.

AU - Kansas, Geoffrey S.

AU - Berndt, Michael C.

AU - Simmons, Paul J.

N1 - Funding Information: This study was supported by grants to J. P. L. and P. J. S. from the Anti-Cancer Foundation of South Australia (31/97) and the National Health and Medical Research Council of Australia (991522) and to G. S. K. from the American Cancer Society (RPG9609703CSM) and the National Institutes of Health (HL58710). J. P. L. is Chargé de Recherche of the Centre National de la Recherche Scientifique. G. S. K. is an Established Investigator of the American Heart Association. The authors wish to thank Dr. L. Lasky (Genentech, San Francisco, CA) for his kind gift of CD62P-IgG 1 and CD4-IgG 1 fusion proteins and Dr L. B. To for the provision of normal human BM samples.

PY - 1999/9

Y1 - 1999/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033198582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033198582&partnerID=8YFLogxK

U2 - 10.1016/S1074-7613(00)80112-0

DO - 10.1016/S1074-7613(00)80112-0

M3 - Article

C2 - 10514015

AN - SCOPUS:0033198582

SN - 1074-7613

VL - 11

SP - 369

EP - 378

JO - Immunity

JF - Immunity

IS - 3

ER -

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

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this