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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-08-2396. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-08-2396v1 101/7/2816    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 Citing Articles via Google Scholar Google Scholar Articles by O'Brien, C. D. Articles by Albelda, S. M. Search for Related Content PubMed PubMed Citation Articles by O'Brien, C. D. Articles by Albelda, S. M. Related Collections Hematopoiesis and Stem Cells Phagocytes Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2003, Vol. 101, No. 7, pp. 2816-2825 PHAGOCYTES PECAM-1-dependent neutrophil transmigration is independent of monolayer PECAM-1 signaling or localization Christopher D. O'Brien, Poay Lim, Jing Sun, and Steven M. Albelda From the Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA. Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), a tyrosine phosphoprotein highly expressed on endothelial cells and leukocytes, is an important component in the regulation of neutrophil transendothelial migration. Engagement of endothelial PECAM-1 activates tyrosine phosphorylation events and evokes prolonged calcium transients, while homophilic engagement of neutrophil PECAM-1 activates leukocyte -integrins. Although PECAM-1 modulates polymorphoneutrophil transmigration via homophilic PECAM-1-PECAM-1 interaction, the mechanisms underlying endothelial PECAM-1 function are unknown. Proposed mechanisms include (1) formation of a haptotactic gradient that "guides" neutrophils to the cell-cell border, (2) service as a "passive ligand" for neutrophil PECAM-1, ultimately mediating activation of neutrophil  integrins, (3) regulation of endothelial calcium influx, and (4) mediation of SH2 protein association, and/or (5) catenin and non-SH2 protein interaction. Utilizing PECAM-1-null "model" endothelial cells (REN cells), we developed a neutrophil transmigration system to study PECAM-1 mutations that specifically disrupt PECAM-1-dependent signaling and/or PECAM-1 cell localization. We report that interleukin-1 (IL-1) elicits PECAM-1-dependent transmigration that requires homophilic PECAM-PECAM-1 engagement, but not heterophilic neutrophil PECAM-1 interactions, and is intercellular adhesion molecule-1 dependent. Conversely, whereas IL-8 and leukotriene-B4-mediated transmigration is PECAM-1-independent, PECAM-1 and IL-8-dependent transmigration represent separable and additive components of cytokine-induced transmigration. Surprisingly, neither monolayer PECAM-1-regulated calcium signaling, cell border localization, nor the PECAM-1 cytoplasmic domain was required for monolayer PECAM-1 regulation of neutrophil transmigration. We conclude that monolayer (endothelial cell) PECAM-1 functions as a passive homophilic ligand for neutrophil PECAM-1, which after engagement leads to neutrophil signal transduction, integrin activation, and ultimately transmigration in a stimulus-specific manner. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Bergom, C. Paddock, C. Gao, T. Holyst, D. K. Newman, and P. J. Newman An alternatively spliced isoform of PECAM-1 is expressed at high levels in human and murine tissues, and suggests a novel role for the C-terminus of PECAM-1 in cytoprotective signaling J. Cell Sci., April 15, 2008; 121(8): 1235 - 1242. [Abstract] [Full Text] [PDF] C. Garnacho, V. Shuvaev, A. Thomas, L. McKenna, J. Sun, M. Koval, S. Albelda, V. Muzykantov, and S. 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Frink, M. A. Choudhry, W. J. Hubbard, L. W. Rue III, K. I. Bland, and I. H. Chaudry Mitochondria play an important role in 17beta-estradiol attenuation of H2O2-induced rat endothelial cell apoptosis Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E585 - E593. [Abstract] [Full Text] [PDF] L. A. Smith, H. Aranda-Espinoza, J. B. Haun, and D. A. Hammer Interplay between Shear Stress and Adhesion on Neutrophil Locomotion Biophys. J., January 15, 2007; 92(2): 632 - 640. [Abstract] [Full Text] [PDF] A. Verbrugge, T. de Ruiter, C. Geest, P. J. Coffer, and L. Meyaard Differential expression of leukocyte-associated Ig-like receptor-1 during neutrophil differentiation and activation J. Leukoc. Biol., April 1, 2006; 79(4): 828 - 836. [Abstract] [Full Text] [PDF] A. O. Eniola, E. F. Krasik, L. A. Smith, G. Song, and D. A. Hammer I-Domain of Lymphocyte Function-Associated Antigen-1 Mediates Rolling of Polystyrene Particles on ICAM-1 under Flow Biophys. 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