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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 (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 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 Social Bookmarking                   What's this? Submitted August 8, 2002 Accepted November 18, 2002 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 Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Philadelphia, PA, USA * Corresponding author; email: christoo{at}mail.med.upenn.edu. 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 PMN 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 IL-1 elicits PECAM-1-dependent transmigration that requires homophilic PECAM-PECAM-1 engagement, but not heterophilic neutrophil PECAM-1 interactions, and is ICAM-1-dependent. Conversely, while IL-8 and LTB4-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(EC) 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Sugimoto, T. Rui, M. Yang, S. Bharwani, O. Handa, N. Yoshida, T. Yoshikawa, and P. R. Kvietys Points of Control Exerted along the Macrophage-Endothelial Cell-Polymorphonuclear Neutrophil Axis by PECAM-1 in the Innate Immune Response of Acute Colonic Inflammation J. Immunol., August 1, 2008; 181(3): 2145 - 2154. [Abstract] [Full Text] [PDF] C. Bergom, C. Paddock, C. Gao, T. Holyst, D. K. Newman, and P. J. 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[Abstract] [Full Text] [PDF] C. D. O'Brien, G. Cao, A. Makrigiannakis, and H. M. DeLisser Role of immunoreceptor tyrosine-based inhibitory motifs of PECAM-1 in PECAM-1-dependent cell migration Am J Physiol Cell Physiol, October 1, 2004; 287(4): C1103 - C1113. [Abstract] [Full Text] [PDF] S. M. Albelda, K. C. Lau, P. Chien, Z.-Y. Huang, E. Arguiris, A. Bohen, J. Sun, J. A. Billet, M. Christofidou-Solomidou, Z. K. Indik, et al. Role for Platelet-Endothelial Cell Adhesion Molecule-1 in Macrophage Fc{gamma} Receptor Function Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 246 - 255. [Abstract] [Full Text] [PDF] D. Feng, J. A. Nagy, K. Pyne, H. F. Dvorak, and A. M. Dvorak Ultrastructural Localization of Platelet Endothelial Cell Adhesion Molecule (PECAM-1, CD31) in Vascular Endothelium J. Histochem. Cytochem., January 1, 2004; 52(1): 87 - 102. [Abstract] [Full Text] [PDF] P. J. Newman and D. K. 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