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The angiogenic factor bFGF impairs leukocyte adhesion and rolling under flow conditions

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Abstract

Recirculation of leukocytes is mediated by the intricately regulated expression of adhesion molecules on both the vessel wall and leukocyte membranes. In the present paper it is demonstrated that tumor angiogenesis factors impair leukocyte rolling and adhesion under flow conditions. Three lines of evidence presented in this paper support this finding; (i) treatment of cultured endothelial cells (EC) with the angiogenic factor basic fibroblast growth factor (bFGF) results in decreased ICAM-1 expression and decreased numbers of adhering leukocytes under flow conditions. (ii) flow induced upregulation of endothelial ICAM-1 in the presence of bFGF does not yield ICAM-1 levels higher than on resting EC. (iii) bFGF decreases the TNFα mediated induction of E-selectin and ICAM-1 expression, resulting in decreased rolling and firm adhesion of leukocytes on the endothelial surface. For ICAM-1 it is demonstrated that bFGF inhibits TNFα induced levels of mRNA, and that this effects is transcriptionally regulated. These findings support our earlier described hypothesis that angiogenic factors are involved in the tumor derived escape mechanism from immune surveillance, since we demonstrate here that these mechanisms are operative under physiologic flow conditions.

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Authors and Affiliations

  1. Department of Internal Medicine and Medical Oncology, Laboratory for Angiogenesis Research, University Hospital Utrecht, Heidelberglaan 100, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands

    Arjan W. Griffioen, Ingrid A.M. Relou, Cora A. Damen, Jacques C. de Graaf & Gerard Groenewegen

  2. Department of Pulmonary Diseases, University Hospital Utrecht, Heidelberglaan 100, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands

    Humberto I. Gallardo Torres

  3. Department of Experimental Medicine, University of L'Aquila, Italy

    Stefano Martinotti

  4. Department of Haematology, University Hospital Utrecht, Heidelberglaan 100, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands

    Jaap J. Zwaginga

Authors
  1. Arjan W. Griffioen
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  2. Ingrid A.M. Relou
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  3. Humberto I. Gallardo Torres
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  4. Cora A. Damen
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  5. Stefano Martinotti
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  6. Jacques C. de Graaf
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  7. Jaap J. Zwaginga
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  8. Gerard Groenewegen
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Griffioen, A.W., Relou, I.A., Gallardo Torres, H.I. et al. The angiogenic factor bFGF impairs leukocyte adhesion and rolling under flow conditions. Angiogenesis 2, 235–243 (1998). https://doi.org/10.1023/A:1009237324501

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