Mac-1 Directly Binds to the Endothelial Protein C-Receptor: A Link between the Protein C Anticoagulant Pathway and InflammationReport as inadecuate




Mac-1 Directly Binds to the Endothelial Protein C-Receptor: A Link between the Protein C Anticoagulant Pathway and Inflammation - Download this document for free, or read online. Document in PDF available to download.

Objective

The endothelial protein C-receptor EPCR is an endothelial transmembrane protein that binds protein C and activated protein C APC with equal affinity, thereby facilitating APC formation. APC has anticoagulant, antiapoptotic and antiinflammatory properties. Soluble EPCR, released by the endothelium, may bind activated neutrophils, thereby modulating cell adhesion. EPCR is therefore considered as a possible link between the anticoagulant properties of protein C and the inflammatory response of neutrophils. In the present study, we aimed to provide proof of concept for a direct binding of EPCR to the β2 –integrin Mac-1 on monocytic cells under static and physiological flow conditions.

Measurements and Main Results

Under static conditions, human monocytes bind soluble EPCR in a concentration dependent manner, as demonstrated by flow cytometry. Binding can be inhibited by specific antibodies anti-EPCR and anti-Mac-1. Specific binding was confirmed by a static adhesion assay, where a transfected Mac-1 expressing CHO cell line Mac-1+ cells bound significantly more recombinant EPCR compared to Mac-1+ cells blocked by anti-Mac-1-antibody and native CHO cells. Under physiological flow conditions, monocyte binding to the endothelium could be significantly blocked by both, anti-EPCR and anti-Mac-1 antibodies in a dynamic adhesion assay at physiological flow conditions. Pre-treatment of endothelial cells with APC drotrecogin alfa diminished monocyte adhesion significantly in a comparable extent to anti-EPCR.

Conclusions

In the present study, we demonstrate a direct binding of Mac-1 on monocytes to the endothelial protein C receptor under static and flow conditions. This binding suggests a link between the protein C anticoagulant pathway and inflammation at the endothelium side, such as in acute vascular inflammation or septicaemia.



Author: Katrin Fink , Hans-Jörg Busch, Natascha Bourgeois, Meike Schwarz, Dennis Wolf, Andreas Zirlik, Karlheinz Peter, Christoph Bode,

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents