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Blood, 11 June 2009, Vol. 113, No. 24, pp. 6246-6257. Prepublished online as a Blood First Edition Paper on February 10, 2009; DOI 10.1182/blood-2008-11-188375. This Article Full Text Full Text (PDF) Supplemental Video All Versions of this Article: blood-2008-11-188375v1 113/24/6246    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 HighWire Citing Articles via CrossRef Google Scholar Articles by Woodfin, A. Articles by Nourshargh, S. PubMed PubMed Citation Articles by Woodfin, A. Articles by Nourshargh, S. Related Collections Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1 Abigail Woodfin1, Mathieu-Benoit Voisin1, Beat A. Imhof2, Elisabetta Dejana3, Britta Engelhardt4, and Sussan Nourshargh1 1 Barts and The London School of Medicine and Dentistry, Queen Mary University of London, William Harvey Research Institute, London, United Kingdom; 2 Centre Medical Universitaire, Geneva, Switzerland; 3 Federazione Italiana per la Ricerca sul Cancro Institute of Molecular Oncology and Department of Biomolecular Sciences and Biotechnologies, School of Sciences, Milan University, Milan, Italy; and 4 Theodor Kocher Institute, University of Bern, Bern, Switzerland Leukocyte transmigration is mediated by endothelial cell (EC) junctional molecules, but the associated mechanisms remain unclear. Here we investigate how intercellular adhesion molecule-2 (ICAM-2), junctional adhesion molecule-A (JAM-A), and platelet endothelial cell adhesion molecule (PECAM-1) mediate neutrophil transmigration in a stimulus-dependent manner (eg, as induced by interleukin-1β [IL-1β] but not tumor necrosis factor- [TNF-]), and demonstrate their ability to act in sequence. Using a cell-transfer technique, transmigration responses of wild-type and TNF- p55/p75 receptor-deficient leukocytes (TNFR–/–) through mouse cremasteric venules were quantified by fluorescence intravital microscopy. Whereas wild-type leukocytes showed a normal transmigration response to TNF- in ICAM-2–/–, JAM-A–/–, and PECAM-1–/– recipient mice, TNFR–/– leukocytes exhibited a reduced transmigration response. Hence, when the ability of TNF- to directly stimulate neutrophils is blocked, TNF-–induced neutrophil transmigration is rendered dependent on ICAM-2, JAM-A, and PECAM-1, suggesting that the stimulus-dependent role of these molecules is governed by the target cell being activated. Furthermore, analysis of the site of arrest of neutrophils in inflamed tissues from ICAM-2–/–, JAM-A–/–, and PECAM-1–/– mice demonstrated that these molecules act sequentially to mediate transmigration. Collectively, the findings provide novel insights into the mechanisms of action of key molecules implicated in leukocyte transmigration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Leukocytes whisper to endothelial guards Francisco Sánchez-Madrid and Olga Barreiro Blood 2009 113: 6048-6049. [Full Text] [PDF] This article has been cited by other articles: W. A. Muller Mechanisms of Transendothelial Migration of Leukocytes Circ. Res., July 31, 2009; 105(3): 223 - 230. [Abstract] [Full Text] [PDF] F. Sanchez-Madrid and O. Barreiro Leukocytes whisper to endothelial guards Blood, June 11, 2009; 113(24): 6048 - 6049. [Full Text] [PDF]

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