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      A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them

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      The Journal of Cell Biology

      The Rockefeller University Press

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          Abstract

          The basic route and mechanisms for leukocyte migration across the endothelium remain poorly defined. We provide definitive evidence for transcellular (i.e., through individual endothelial cells) diapedesis in vitro and demonstrate that virtually all, both para- and transcellular, diapedesis occurs in the context of a novel “cuplike” transmigratory structure. This endothelial structure was comprised of highly intercellular adhesion molecule-1– and vascular cell adhesion molecule-1–enriched vertical microvilli-like projections that surrounded transmigrating leukocytes and drove redistribution of their integrins into linear tracks oriented parallel to the direction of diapedesis. Disruption of projections was highly correlated with inhibition of transmigration. These findings suggest a novel mechanism, the “transmigratory cup”, by which the endothelium provides directional guidance to leukocytes for extravasation.

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          Most cited references 38

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          Atherosclerosis--an inflammatory disease.

           R. Ross,  Paul O'Byrne (1999)
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            Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm.

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              Transcytosis and surface presentation of IL-8 by venular endothelial cells.

               John Moore,  S Neil,  J Wintle (1997)
              Chemokines have been convincingly implicated in actuating inflammatory leukocyte emigration. To affect the circulating leukocytes, tissue-derived chemokines have to traverse the endothelial cells (ECs). This was thought to be accomplished by chemokine diffusion through the intercellular gaps. On the contrary, we show by electron microscopy that the prototype chemokine IL-8 is internalized by venular ECs abluminally and transcytosed to the luminal surface. Here, it is presented to the adherent leukocytes on the EC membrane, predominantly in association with the EC projections. The intact C terminus of IL-8, the molecule's "immobilization" domain, is required for the EC binding, transcytosis, and consequently, the in vivo proemigratory activity of IL-8, indicating that the described subcellular interactions of IL-8 with the ECs are functionally relevant.
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                Author and article information

                Journal
                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                25 October 2004
                : 167
                : 2
                : 377-388
                Affiliations
                The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA 02115
                Author notes

                Correspondence to Timothy A. Springer: springeroffice@ 123456cbr.med.harvard.edu

                Article
                200404129
                10.1083/jcb.200404129
                2172560
                15504916
                Copyright © 2004, The Rockefeller University Press
                Categories
                Research Articles
                Article

                Cell biology

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