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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2003-01-0003. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0003v1 102/1/169    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 Gao, C. Articles by Newman, P. J. Search for Related Content PubMed PubMed Citation Articles by Gao, C. Articles by Newman, P. J. Related Collections Apoptosis Cell Adhesion and Motility Signal Transduction Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2003, Vol. 102, No. 1, pp. 169-179 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY PECAM-1 functions as a specific and potent inhibitor of mitochondrial-dependent apoptosis Cunji Gao, Weiyong Sun, Melpo Christofidou-Solomidou, Motoshi Sawada, Debra K. Newman, Carmen Bergom, Steven M. Albelda, Shigemi Matsuyama, and Peter J. Newman From the Laboratories of PECAM-1 Research and Cell Biology, Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee; Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia; and the Departments of Microbiology, Pharmacology, and Cellular Biology and the Cardiovascular Center, Medical College of Wisconsin, Milwaukee. Programmed cell death, or apoptosis, is a tightly regulated, naturally occurring process by which damaged or unwanted cells are removed. Dysregulated apoptosis has been implicated in a variety of pathophysiological conditions, including degenerative diseases, tissue remodeling, and tumorogenesis. The decision to live or die results from integration of numerous environmental signals transmitted by specific classes of cell surface receptors that bind hormones, growth factors, or components of the extracellular matrix. Here we show that platelet endothelial cell adhesion molecule-1 (PECAM-1), a homophilic-binding member of the immunoreceptor tyrosine-based inhibitory motif (ITIM) family of inhibitory receptors, functions prominently to inhibit apoptosis in naturally occurring vascular cells subjected to apoptotic stimuli. Murine endothelial cells and human T lymphocytes lacking PECAM-1 were found to be far more sensitive than their PECAM-1—expressing counterparts to multiple death signals that stimulate Bax, a multidomain, proapoptotic member of the Bcl-2 family that plays a central role in mitochondrial dysfunction-dependent apoptosis. In addition, PECAM-1 markedly suppressed Bax overexpression—induced cytochrome c release, caspase activation, and nuclear fragmentation. Amino acid substitutions within PECAM-1's extracellular homophilic binding domain, or within its cytoplasmic ITIM, completely abolished PECAM-1—mediated cytoprotection. Taken together, these data implicate PECAM-1 as a novel and potent suppressor of Bax-mediated apoptosis and suggest that members of the immunoglobulin gene (Ig) superfamily, like cell surface integrins, may also transmit survival signals into blood and vascular cells. (Blood. 2003;102:169-179) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: PECAM-1/CD31 provides survival signals to suppress apoptosis Denise E. Jackson Blood 2003 102: 3-4. [Full Text] [PDF] 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] T. S. Dhanjal, C. Pendaries, E. A. Ross, M. K. Larson, M. B. Protty, C. D. 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