E-selectin and very late activation antigen-4 mediate adhesion of hematopoietic progenitor cells to bone marrow endothelium |
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Authors: | 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 |
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Affiliation: | (1) Department of Experimental Immunohematology, CLB and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands e-mail: schoot@clb.nl Tel: +31-20-5123377 Fax: +31-20-5123474, NL;(2) Department of Internal Medicine, University Hospital Utrecht, Utrecht, The Netherlands, NL;(3) Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands, NL;(4) Department of Medical Oncology, Academic Hospital of the Free University, Amsterdam, The Netherlands, NL |
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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. Received: 26 April 1999 / Accepted: 8 February 2000 |
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Keywords: | Bone marrow endothelium CD34+ hematopoietic progenitor cells Adhesion E-selectin VLA-4 |
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