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

S Kurosawa, CT Esmon… - The Journal of …, 2000 - journals.aai.org
S Kurosawa, CT Esmon, DJ Stearns-Kurosawa
The Journal of Immunology, 2000journals.aai.org
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 …
Abstract
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 β 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 β 2 integrin suggests that there may be a link between the protein C anticoagulant pathway and neutrophil functions.
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