edoc

Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling

Bertozzi, Cara C. and Schmaier, Alec A. and Mericko, Patricia and Hess, Paul R. and Zou, Zhiying and Chen, Mei and Chen, Chiu-Yu and Xu, Bin and Lu, Min-min and Zhou, Diane and Sebzda, Eric and Santore, Matthew T. and Merianos, Demetri J. and Stadtfeld, Matthias and Flake, Alan W. and Graf, Thomas and Skoda, Radek and Maltzman, Jonathan S. and Koretzky, Gary A. and Kahn, Mark L.. (2010) Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling. Blood, Vol. 116, H. 4. pp. 661-670.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6005170

Downloads: Statistics Overview

Abstract

Although platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK-SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre-mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76-dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Hämatologie > Molekulare Medizin (Skoda)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Hämatologie > Molekulare Medizin (Skoda)
UniBasel Contributors:Skoda, Radek C.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society of Hematology
ISSN:1528-0020
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:21 Jun 2013 12:29
Deposited On:21 Jun 2013 12:21

Repository Staff Only: item control page