Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis.
BACKGROUND
We recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation.


METHODS
Circulating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardiovascular disease and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. The plasminogen activators on microparticles were identified by flow cytometry and enzyme-linked immunosorbent assays; their capacity to generate plasmin was quantified with a chromogenic assay and their fibrinolytic activity was determined by zymography.


RESULTS
Circulating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content of urokinase-type plasminogen activator and/or tissue plasminogen activator. Using distinct microparticle subpopulations, we demonstrated that plasmin is generated on endothelial and leukocyte microparticles, but not on microparticles of platelet or erythrocyte origin. Leukocyte-derived microparticles bear urokinase-type plasminogen activator and its receptor whereas endothelial microparticles carry tissue plasminogen activator and tissue plasminogen activator/inhibitor complexes.


CONCLUSIONS
Endothelial and leukocyte microparticles, bearing respectively tissue plasminogen activator or urokinase-type plasminogen activator, support a part of the fibrinolytic activity in the circulation which is modulated in pathological settings. Awareness of this blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view of the role of microparticles in the hemostatic equilibrium.
Aix Marseille Université, INSERM UMR-S1076, UFR de Pharmacie, Marseille, France.
Romaric
R
Lacroix
Laurent
L
Plawinski
Stéphane
S
Robert
Loïc
L
Doeuvre
Florence
F
Sabatier
Sara
S
Martinez de Lizarrondo
Anna
A
Mezzapesa
Francine
F
Anfosso
Aurelie S
AS
Leroyer
Pascale
P
Poullin
Noémie
N
Jourde
Makon-Sébastien
MS
Njock
Chantal M
CM
Boulanger
Eduardo
E
Anglés-Cano
Françoise
F
Dignat-George
D002318:Cardiovascular Diseases / Q000097:blood* / Q000473:pathology; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000473:pathology; D012077:Renal Artery / Q000166:cytology / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator