Mobolization and homing of peripheral blood progenitors is related to reversible downregulation of α4β1 integrin expression and function

Felipe Prosper, David Stroncek, James B. McCarthy, Catherine M. Verfaillie

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Despite the wide use of mobilized peripheral blood (PB) progenitor cells (PBPC) for clinical transplantation the mechanism(s) underlying their mobilization and subsequent engraftment are still unknown. We compared the adhesive phenotype of CD34+ colony-forming cells (CFC) in bone marrow (BM) and PB of normal donors before and after administration of granulocyte colony-stimulating factor (G-CSF) for 5 d. G-CSF-mobilized PB CFC cells adhered significantly less to BM stroma, fibronectin, and to the α4β1 binding fibronectin peptide, CS1, because of decreased expression of the α4 integrin. Since incubation of BM CD34+ cells for 4 d with G-CSF at concentrations found in serum of G-CSF-treated individuals did not affect α4-dependent adhesion, G-CSF may not be directly responsible for the decreased α4-mediated adhesion of PB CFC. Culture of G-CSF-mobilized PB CD34+ cells with cytokines at concentrations found in BM stromal cultures upregulated α4 expression and restored adhesion of mobilized PB CFC to stroma, fibronectin, and CS1. Adhesion of cultured, mobilized PB CFC to stroma and CS1 could not be further upregulated by the β1 activating antibody, 8A2. This indicates acquisition of a maximally activated α4β1 integrin once PB CFC have been removed from the in vivo mobilizing milieu. Thus, decreased α4 expression on CD34+ CFC in PB may be responsible for the aberrant circulation of mobilized PB CD34+ cells. Reexpression of a maximally activated α4β1 integrin on mobilized PB CFC removed from the mobilizing in vivo milieu may contribute to the early engraftment of mobilized PBPC.

Original languageEnglish (US)
Pages (from-to)2456-2467
Number of pages12
JournalJournal of Clinical Investigation
Volume101
Issue number11
DOIs
StatePublished - Jun 1 1998

Keywords

  • Adhesion receptors
  • Bone marrow transplant
  • Growth factors
  • Homing
  • Mobilization

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