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 critical component of the host response to inflammatory stimuli. The most recent member of this pathway is the endothelial protein C receptor (EPCR), a type I transmembrane protein with homology to CD1d/MHC class I proteins. EPCR accelerates formation of activated protein C, a potent anticoagulant and antiinflammatory agent. The current study demonstrates that soluble EPCR binds to PMA-activated neutrophils. Using affinity chromatography, binding studies with purified components, and/or blockade with specific Abs, it was found that soluble EPCR binds to proteinase-3 (PR3), a neutrophil granule proteinase. Furthermore, soluble EPCR binding to neutrophils was partially dependent on Mac-1 (CD11b/CD18), a beta(2) integrin involved in neutrophil signaling, and cell-cell adhesion events. PR3 is involved in multiple diverse processes, including hemopoietic proliferation, antibacterial activity, and autoimmune-mediated vasculitis. The observation that soluble EPCR binds to activated neutrophils via PR3 and a beta(2) integrin suggests that there may be a link between the protein C anticoagulant pathway and neutrophil functions.
Kurosawa
S
S
Cardiovascular Biology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Esmon
C T
CT
Stearns-Kurosawa
D J
DJ
D001779:Blood Coagulation Factors; D018821:CD18 Antigens / Q000502:physiology*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000502:physiology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D011485:Protein Binding; D011486:Protein C / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000502:physiology*; D012995:Solubility
D001779:Blood Coagulation Factors; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D011486:Protein C; D011956:Receptors, Cell Surface; C091963:activated protein C receptor; D012697:Serine Endopeptidases