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Blood, 8 October 2009, Vol. 114, No. 15, pp. 3335-3342. Prepublished online as a Blood First Edition Paper on August 6, 2009; DOI 10.1182/blood-2009-01-198945. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-01-198945v1 114/15/3335    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Urbinati, C. Articles by Rusnati, M. PubMed PubMed Citation Articles by Urbinati, C. Articles by Rusnati, M. Related Collections Immunobiology Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY HIV-1 Tat and heparan sulfate proteoglycan interaction: a novel mechanism of lymphocyte adhesion and migration across the endothelium Chiara Urbinati1, Stefania Nicoli1, Mauro Giacca2, Guido David3, Simona Fiorentini4, Arnaldo Caruso4, Massimo Alfano5, Luca Cassetta5, Marco Presta1, and Marco Rusnati1 1 Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, Medical School, University of Brescia, Brescia, Italy; 2 Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy; 3 Department of Human Genetics, University of Leuven and Flanders Institute for Biotechnology, Leuven, Belgium; 4 Section of Microbiology, Department of Experimental and Applied Medicine, School of Medicine, Brescia, Italy; and 5 AIDS Immunopathogenesis Unit, Department of Immunology and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy The HIV-1 transactivating factor Tat accumulates on the surface of endothelium by interacting with heparan sulfate proteoglycans (HSPGs). Tat also interacts with B-lymphoid Namalwa cells but only when these overexpress HSPGs after syndecan-1 cDNA transfection (SYN-NCs). Accordingly, SYN-NCs, but not mock-transfected cells, adhere to endothelial cells (ECs) when Tat is bound to the surface of either one of the 2 cell types or when SYN-NCs are transfected with a Tat cDNA. Moreover, endogenously produced Tat bound to cell-surface HSPGs mediates cell adhesion of HIV+ ACH-2 lymphocytes to the endothelium. This heterotypic lymphocyte-EC interaction is prevented by HSPG antagonist or heparinase treatment, but not by integrin antagonists and requires the homodimerization of Tat protein. Tat tethered to the surface of SYN-NCs or of peripheral blood monocytes from healthy donors promotes their transendothelial migration in vitro in response to CXCL12 or CCL5, respectively, and SYN-NC extravasation in vivo in a zebrafish embryo model of inflammation. In conclusion, Tat homodimers bind simultaneously to HSPGs expressed on lymphoid and EC surfaces, leading to HSPG/Tat-Tat/HSPG quaternary complexes that physically link HSPG-bearing lymphoid cells to the endothelium, promoting their extravasation. These data provide new insights about how lymphoid cells extravasate during HIV infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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