PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: Evidence for cooperation between E-selectin ligands and α4 integrin

Yoshio Katayama, Andrés Hidalgo, Barbara C. Furie, Dietmar Vestweber, Bruce Furie, Paul S. Frenette

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

The nature and exact function of selectin ligands involved in hematopoietic progenitor cell (HPC) homing to the bone marrow (BM) are unclear. Using murine progenitor homing assays in lethally irradiated recipients, we found that the P-selectin glycoprotein ligand-1 (PSGL-1) plays a partial role in HPC homing to the BM (a reduction of about 35% when the P-selectin binding region is blocked). Blockade of both PSGL-1 and α4 integrin did not further enhance the effect of anti-α4 integrin (a reduction of about 55%). We suspected that E-selectin ligands might contribute to the remaining homing activity. To test this hypothesis, HPC homing assays were carried out in E-selectin-deficient recipients and revealed a profound alteration in HPC homing when E-selectin and α4 integrin were inactivated (> 90% reduction). Competitive assays to test homing of long-term repopulating stem cells revealed a drastic reduction (> 99%) of the homed stem cell activity when both α4 integrin and E-selectin functions were absent. Further homing studies with PSGL-1-deficient HPCs pretreated with anti-α4 integrin antibody revealed that PSGL-1 contributes to approximately 60% of E-selectin ligand-mediated homing activity. Our results thus underscore a major difference between mature myeloid cells and immature stem/ progenitor cells in that E-selectin ligands cooperate with α4 integrin rather than P-selectin ligands.

Original languageEnglish (US)
Pages (from-to)2060-2067
Number of pages8
JournalBlood
Volume102
Issue number6
DOIs
StatePublished - Sep 15 2003
Externally publishedYes

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E-Selectin
Integrins
Bone
Bone Marrow
Hematopoietic Stem Cells
Ligands
Stem Cells
Stem cells
Assays
P-Selectin
Selectins
Myeloid Cells
P-selectin ligand protein
Antibodies

ASJC Scopus subject areas

  • Hematology

Cite this

PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow : Evidence for cooperation between E-selectin ligands and α4 integrin. / Katayama, Yoshio; Hidalgo, Andrés; Furie, Barbara C.; Vestweber, Dietmar; Furie, Bruce; Frenette, Paul S.

In: Blood, Vol. 102, No. 6, 15.09.2003, p. 2060-2067.

Research output: Contribution to journalArticle

Katayama, Yoshio ; Hidalgo, Andrés ; Furie, Barbara C. ; Vestweber, Dietmar ; Furie, Bruce ; Frenette, Paul S. / PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow : Evidence for cooperation between E-selectin ligands and α4 integrin. In: Blood. 2003 ; Vol. 102, No. 6. pp. 2060-2067.
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abstract = "The nature and exact function of selectin ligands involved in hematopoietic progenitor cell (HPC) homing to the bone marrow (BM) are unclear. Using murine progenitor homing assays in lethally irradiated recipients, we found that the P-selectin glycoprotein ligand-1 (PSGL-1) plays a partial role in HPC homing to the BM (a reduction of about 35{\%} when the P-selectin binding region is blocked). Blockade of both PSGL-1 and α4 integrin did not further enhance the effect of anti-α4 integrin (a reduction of about 55{\%}). We suspected that E-selectin ligands might contribute to the remaining homing activity. To test this hypothesis, HPC homing assays were carried out in E-selectin-deficient recipients and revealed a profound alteration in HPC homing when E-selectin and α4 integrin were inactivated (> 90{\%} reduction). Competitive assays to test homing of long-term repopulating stem cells revealed a drastic reduction (> 99{\%}) of the homed stem cell activity when both α4 integrin and E-selectin functions were absent. Further homing studies with PSGL-1-deficient HPCs pretreated with anti-α4 integrin antibody revealed that PSGL-1 contributes to approximately 60{\%} of E-selectin ligand-mediated homing activity. Our results thus underscore a major difference between mature myeloid cells and immature stem/ progenitor cells in that E-selectin ligands cooperate with α4 integrin rather than P-selectin ligands.",
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