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 journalArticle

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
Publication statusPublished - 2000
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Rood, P. M. L., Dercksen, M. W., Cazemier, H., Kerst, J. M., Von dem Borne, A. E. G. K., Gerritsen, W. R., & Van der Schoot, C. E. (2000). E-selectin and very late activation antigen-4 mediate adhesion of hematopoietic progenitor cells to bone marrow endothelium. Annals of Hematology, 79(9), 477-484.