Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation.
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Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation. / Darbousset, Roxane; Thomas, Grace M; Mezouar, Soraya; Frère, Corinne; Bonier, Rénaté; Mackman, Nigel; Renné, Thomas; Dignat-George, Françoise; Dubois, Christophe; Panicot-Dubois, Laurence.
in: BLOOD, Jahrgang 120, Nr. 10, 10, 2012, S. 2133-2143.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation.
AU - Darbousset, Roxane
AU - Thomas, Grace M
AU - Mezouar, Soraya
AU - Frère, Corinne
AU - Bonier, Rénaté
AU - Mackman, Nigel
AU - Renné, Thomas
AU - Dignat-George, Françoise
AU - Dubois, Christophe
AU - Panicot-Dubois, Laurence
PY - 2012
Y1 - 2012
N2 - For a long time, blood coagulation and innate immunity have been viewed as interrelated responses. Recently, the presence of leukocytes at the sites of vessel injury has been described. Here we analyzed interaction of neutrophils, monocytes, and platelets in thrombus formation after a laser-induced injury in vivo. Neutrophils immediately adhered to injured vessels, preceding platelets, by binding to the activated endothelium via leukocyte function antigen-1-ICAM-1 interactions. Monocytes rolled on a thrombus 3 to 5 minutes postinjury. The kinetics of thrombus formation and fibrin generation were drastically reduced in low tissue factor (TF) mice whereas the absence of factor XII had no effect. In vitro, TF was detected in neutrophils. In vivo, the inhibition of neutrophil binding to the vessel wall reduced the presence of TF and diminished the generation of fibrin and platelet accumulation. Injection of wild-type neutrophils into low TF mice partially restored the activation of the blood coagulation cascade and accumulation of platelets. Our results show that the interaction of neutrophils with endothelial cells is a critical step preceding platelet accumulation for initiating arterial thrombosis in injured vessels. Targeting neutrophils interacting with endothelial cells may constitute an efficient strategy to reduce thrombosis.
AB - For a long time, blood coagulation and innate immunity have been viewed as interrelated responses. Recently, the presence of leukocytes at the sites of vessel injury has been described. Here we analyzed interaction of neutrophils, monocytes, and platelets in thrombus formation after a laser-induced injury in vivo. Neutrophils immediately adhered to injured vessels, preceding platelets, by binding to the activated endothelium via leukocyte function antigen-1-ICAM-1 interactions. Monocytes rolled on a thrombus 3 to 5 minutes postinjury. The kinetics of thrombus formation and fibrin generation were drastically reduced in low tissue factor (TF) mice whereas the absence of factor XII had no effect. In vitro, TF was detected in neutrophils. In vivo, the inhibition of neutrophil binding to the vessel wall reduced the presence of TF and diminished the generation of fibrin and platelet accumulation. Injection of wild-type neutrophils into low TF mice partially restored the activation of the blood coagulation cascade and accumulation of platelets. Our results show that the interaction of neutrophils with endothelial cells is a critical step preceding platelet accumulation for initiating arterial thrombosis in injured vessels. Targeting neutrophils interacting with endothelial cells may constitute an efficient strategy to reduce thrombosis.
KW - Animals
KW - Mice
KW - Cell Movement
KW - Cell Count
KW - Cell Communication
KW - Lasers
KW - Cell Adhesion
KW - Intercellular Adhesion Molecule-1/metabolism
KW - Platelet Count
KW - Monocytes/cytology
KW - Fibrin/metabolism
KW - Blood Coagulation
KW - Blood Platelets/cytology
KW - Blood Vessels/injuries/metabolism/pathology
KW - Endothelial Cells/metabolism/pathology
KW - Endothelium, Vascular/metabolism/pathology
KW - Factor XII/metabolism
KW - Factor XII Deficiency/genetics/metabolism
KW - Neutrophils/cytology/metabolism/transplantation
KW - Thromboplastin/deficiency/genetics
KW - Thrombosis/metabolism
KW - Animals
KW - Mice
KW - Cell Movement
KW - Cell Count
KW - Cell Communication
KW - Lasers
KW - Cell Adhesion
KW - Intercellular Adhesion Molecule-1/metabolism
KW - Platelet Count
KW - Monocytes/cytology
KW - Fibrin/metabolism
KW - Blood Coagulation
KW - Blood Platelets/cytology
KW - Blood Vessels/injuries/metabolism/pathology
KW - Endothelial Cells/metabolism/pathology
KW - Endothelium, Vascular/metabolism/pathology
KW - Factor XII/metabolism
KW - Factor XII Deficiency/genetics/metabolism
KW - Neutrophils/cytology/metabolism/transplantation
KW - Thromboplastin/deficiency/genetics
KW - Thrombosis/metabolism
M3 - SCORING: Journal article
VL - 120
SP - 2133
EP - 2143
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 10
M1 - 10
ER -
