The soluble endothelial protein C receptor binds to activated neutrophils:Involvement of proteinase-3 and CD11b/CD18

The protein C pathway is a primary regulator of blood coagulation and a cri tical component of the host response to inflammatory stimuli. The most rece nt member of this pathway is the endothelial protein C receptor (EPCR), a t ype I transmembrane protein with homology to CD1d/MHC class I proteins. EPC R accelerates formation of activated protein C, a potent anticoagulant and antiinflammatory agent. The current study demonstrates that soluble EPCR bi nds to PMA-activated neutrophils, Using affinity chromatography, binding st udies with purified components, and/or blockade with specific Abs, it was f ound that soluble EPCR binds to proteinase-3 (PR3), a neutrophil granule pr oteinase, Furthermore, soluble EPCR binding to neutrophils was partially de pendent on Mac-1 (CD11b/CD18), a beta(2) integrin involved in neutrophil si gnaling, and cell-cell adhesion events, PR3 is involved in multiple diverse processes, including hemopoietic proliferation, antibacterial activity, an d autoimmune-mediated vasculitis. The observation that soluble EPCR binds t o activated neutrophils via PR3 and a beta(2) integrin suggests that there may be a link between the protein C anticoagulant pathway and neutrophil fu nctions.