title: Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation.
abstract: 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.
authors: Campus Santé, Aix Marseille Université, Marseille, France.
authors: Roxane
authors: R
authors: Darbousset
authors: Grace M
authors: GM
authors: Thomas
authors: Soraya
authors: S
authors: Mezouar
authors: Corinne
authors: C
authors: Frère
authors: Rénaté
authors: R
authors: Bonier
authors: Nigel
authors: N
authors: Mackman
authors: Thomas
authors: T
authors: Renné
authors: Françoise
authors: F
authors: Dignat-George
authors: Christophe
authors: C
authors: Dubois
authors: Laurence
authors: L
authors: Panicot-Dubois
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000166:cytology; D001808:Blood Vessels / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication; D002452:Cell Count; D002465:Cell Movement; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005174:Factor XII / Q000378:metabolism; D005175:Factor XII Deficiency / Q000235:genetics / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007834:Lasers; D051379:Mice; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D010976:Platelet Count; D013925:Thromboplastin / Q000172:deficiency / Q000235:genetics*; D013927:Thrombosis / Q000378:metabolism*
chemical_list: D018799:Intercellular Adhesion Molecule-1; D005174:Factor XII; D005337:Fibrin; D013925:Thromboplastin