E-selectin and very late activation antigen-4 mediate adhesion of hematopoietic progenitor cells to bone marrow endothelium

P. M.L. Rood, M. W. Dercksen, H. Cazemier, J. M. Kerst, A. E.G.K. von dem Borne, W. R. Gerritsen, C. E. van der Schoot

Research output: Contribution to journalArticlepeer-review

Abstract

Adhesion of CD34 + hematopoietic progenitor cells (HPCs) to sinusoidal endothelium probably plays a key role in homing of transplanted CD34+ HPCs to the bone marrow (BM). We have investigated the role of various adhesion molecules in the interaction of purified CD34+ HPCs derived from BM or peripheral blood (PB) and a human BM-derived endothelial cell line. Adhesion of CD34+ HPCs to endothelial cells was measured with the use of a double-color flow microfluorimetric adhesion assay. In this assay, adhesion is measured under stirring conditions, simulating blood flow in sinusoidal marrow vessels. Adhesion of PB CD34+ cells to human BM endothelial cells (HBMECs) was observed only after interleukin (IL)-1β prestimulation of the endothelial cells. This adhesion was strongly increased after addition of phorbol-myristate acetate (PMA). Adhesion of PB CD34+ cells to IL-1β-prestimulated HBMECs was inhibited by blocking monoclonal antibodies (mAbs) against E-selectin and by neuraminidase treatment of the PB CD34+ cells. mAbs against very late activation antigen (VLA)-4 inhibited adhesion only when the E-selectin-mediated interaction was prevented. No clear inhibiting effect was found with blocking mAbs against β2-integrins. Stimulation with the β1-integrin-activating mAb, 8A2, induced adhesion of CD34+ cells to endothelial cells. In conclusion, stimulation of both endothelial cells and CD34+ HPCs is necessary for adhesion of CD34+ HPCs to endothelial cells. We furthermore demonstrated that E-selectin and VLA-4 mediated this adhesion.

Original languageEnglish (US)
Pages (from-to)477-484
Number of pages8
JournalAnnals of hematology
Volume79
Issue number9
DOIs
StatePublished - Jan 1 2000

Keywords

  • Adhesion
  • Bone marrow endothelium
  • CD34 hematopoietic progenitor cells
  • E-selectin
  • VLA-4

ASJC Scopus subject areas

  • Hematology

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