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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.
Submitted October 15, 2003
Accepted January 27, 2004
Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated high endothelial venule (HEV) endothelial cells outside of the lymphoid tissue microenvironment
Delphine-Armelle LACORRE, Espen S BAEKKEVOLD, Ignacio GARRIDO, Per BRANDTZAEG, Guttorm HARALDSEN, Francois AMALRIC, and Jean-Philippe GIRARD*
Laboratoire de Biologie Vasculaire- Equipe Labellisee 'LA LIGUE 2003', Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, Toulouse, France
Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Oslo, Norway
* Corresponding author; email: Jean-Philippe.Girard{at}ipbs.fr.
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 identify endothelial cell genes that are under control of the local microenvironment. By comparing post-capillary high endothelial venules (HEV) endothelial cells (HEVEC), freshly isolated from human tonsils without any cell culture step, with HEVEC cultured for two days, we found that HEVEC rapidly lost their specialized characteristics when isolated from the lymphoid tissue microenvironment. Striking changes occurred as early as after 48 h, with complete loss of the post-capillary venule-specific Duffy Antigen Receptor for Chemokines (DARC) and the HEV-specific fucosyltransferase Fuc-TVII. DNA microarray analysis identified several other candidate HEV genes that were rapidly downregulated ex vivo, including type-XV collagen which we characterized as a novel abundant HEV transcript in situ. Together, our results demonstrate that both blood vessel type- and tissue-specific characteristics of endothelial cells are under control of their microenvironment. Therefore, even short-term primary cultures of human endothelial cells may not mimic adequately the differentiated endothelial cell phenotypes existing in vivo.
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