title: Laser-induced endothelial cell activation supports fibrin formation.
abstract: Laser-induced vessel wall injury leads to rapid thrombus formation in an animal thrombosis model. The target of laser injury is the endothelium. We monitored calcium mobilization to assess activation of the laser-targeted cells. Infusion of Fluo-4 AM, a calcium-sensitive fluorochrome, into the mouse circulation resulted in dye uptake in the endothelium and circulating hematopoietic cells. Laser injury in mice treated with eptifibatide to inhibit platelet accumulation resulted in rapid calcium mobilization within the endothelium. Calcium mobilization correlated with the secretion of lysosomal-associated membrane protein 1, a marker of endothelium activation. In the absence of eptifibatide, endothelium activation preceded platelet accumulation. Laser activation of human umbilical vein endothelial cells loaded with Fluo-4 resulted in a rapid increase in calcium mobilization associated cell fluorescence similar to that induced by adenosine diphosphate (10 μM) or thrombin (1 U/mL). Laser activation of human umbilical vein endothelial cells in the presence of corn trypsin inhibitor treated human plasma devoid of platelets and cell microparticles led to fibrin formation that was inhibited by an inhibitory monoclonal anti-tissue factor antibody. Thus laser injury leads to rapid endothelial cell activation. The laser activated endothelial cells can support formation of tenase and prothrombinase and may be a source of activated tissue factor as well.
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Ben T
authors.initials: BT
authors.lastname: Atkinson
authors.forename: Reema
authors.initials: R
authors.lastname: Jasuja
authors.forename: Vivien M
authors.initials: VM
authors.lastname: Chen
authors.forename: Prathima
authors.initials: P
authors.lastname: Nandivada
authors.forename: Bruce
authors.initials: B
authors.lastname: Furie
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Furie
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism* / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism / Q000528:radiation effects; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D007834:Lasers; D051379:Mice; D008810:Mice, Inbred C57BL; D013927:Thrombosis
chemical_list: D005337:Fibrin; D002118:Calcium