Delayed mortality and attenuated thrombocytopenia associated with severe malaria in urokinase- and urokinase receptor-deficient mice.

Détails

ID Serval
serval:BIB_21A07D69DCA5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Delayed mortality and attenuated thrombocytopenia associated with severe malaria in urokinase- and urokinase receptor-deficient mice.
Périodique
Infection and Immunity
Auteur(s)
Piguet P.F., Da Laperrousaz C., Vesin C., Tacchini-Cottier F., Senaldi G., Grau G.E.
ISSN
0019-9567 (Print)
ISSN-L
0019-9567
Statut éditorial
Publié
Date de publication
2000
Volume
68
Numéro
7
Pages
3822-3829
Langue
anglais
Résumé
We explored the role of urokinase and tissue-type plasminogen activators (uPA and tPA), as well as the uPA receptor (uPAR; CD87) in mouse severe malaria (SM), using genetically deficient (-/-) mice. The mortality resulting from Plasmodium berghei ANKA infection was delayed in uPA(-/-) and uPAR(-/-) mice but was similar to that of the wild type (+/+) in tPA(-/-) mice. Parasitemia levels were similar in uPA(-/-), uPAR(-/-), and +/+ mice. Production of tumor necrosis factor, as judged from the plasma level and the mRNA levels in brain and lung, was markedly increased by infection in both +/+ and uPAR(-/-) mice. Breakdown of the blood-brain barrier, as evidenced by the leakage of Evans Blue, was similar in +/+ and uPAR(-/-) mice. SM was associated with a profound thrombocytopenia, which was attenuated in uPA(-/-) and uPAR(-/-) mice. Administration of aprotinin, a plasmin antagonist, also delayed mortality and attenuated thrombocytopenia. Platelet trapping in cerebral venules or alveolar capillaries was evident in +/+ mice but absent in uPAR(-/-) mice. In contrast, macrophage sequestration in cerebral venules or alveolar capillaries was evident in both +/+ and uPAR(-/-) mice. Polymorphonuclear leukocyte sequestration in alveolar capillaries was similar in +/+ and uPAR(-/-) mice. These results demonstrate that the uPAR deficiency attenuates the severity of SM, probably by its important role in platelet kinetics and trapping. These results therefore suggest that platelet sequestration contributes to the pathogenesis of SM.
Mots-clé
Animals, Aprotinin/pharmacology, Blood Platelets/pathology, Blood-Brain Barrier, Cell Survival, Fibrinogen/metabolism, Kinetics, Lung/pathology, Malaria/complications, Malaria/genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Organ Size, Parasitemia/complications, Parasitemia/genetics, Plasmodium berghei, RNA, Messenger/genetics, RNA, Messenger/metabolism, Receptors, Cell Surface/deficiency, Receptors, Cell Surface/genetics, Receptors, Urokinase Plasminogen Activator, Spleen/pathology, Thrombocytopenia/etiology, Tissue Plasminogen Activator/deficiency, Tissue Plasminogen Activator/genetics, Tumor Necrosis Factor-alpha/genetics, Urokinase-Type Plasminogen Activator/deficiency, Urokinase-Type Plasminogen Activator/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:09
Dernière modification de la notice
20/08/2019 13:58
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