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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4164-4172.
Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-10-3537.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated high endothelial venule endothelial cells outside the lymphoid tissue microenvironment
Delphine-Armelle Lacorre,
Espen S. Baekkevold,
Ignacio Garrido,
Per Brandtzaeg,
Guttorm Haraldsen,
François Amalric, and
Jean-Philippe Girard
From the Laboratoire de Biologie Vasculaire, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique (CNRS) UMR 5089, Toulouse, France; and the Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Riks-hospitalet, Oslo, Norway.
Endothelial cells display remarkable heterogeneity in different organs and vascular beds. Although many studies suggest that tissues "speak" to endothelial cells, endothelial cell diversity remains poorly characterized at the molecular level. Here, we describe a novel strategy to characterize tissue-specific endothelial cell phenotypes and to identify endothelial cell genes that are under the control of the local microenvironment. By comparing post-capillary high endothelial venule endothelial cells (HEVECs), freshly isolated from human tonsils without any cell culture step, with HEVECs cultured for 2 days, we found that HEVECs rapidly lost their specialized characteristics when isolated from the lymphoid tissue microenvironment. Striking changes occurred as early as after 48 hours, with complete loss of the postcapillary venule–specific Duffy antigen receptor for chemokines (DARCs) and the HEV-specific fucosyltransferase Fuc-TVII. DNA microarray analysis identified several other candidate HEV genes that were rapidly down-regulated ex vivo, including type XV collagen, which we characterized as a novel, abundant HEV transcript in situ. Together, our results demonstrate that blood vessel type–specific and tissue-specific characteristics of endothelial cells are under the control of their microenvironment. Therefore, even short-term primary cultures of human endothelial cells may not adequately mimic the differentiated endothelial cell phenotypes existing in vivo.
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