Linked Life Data

11164103

Source:http://linkedlifedata.com/resource/pubmed/id/11164103

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pubmed-article:11164103pubmed:abstractTextA sufficiently high dose of thrombopoietin to overcome initial c-mpl-mediated clearance stimulates hematopoietic reconstitution following myelosuppressive treatment. We studied the efficacy of thrombopoietin on survival after supralethal total body irradiation (9 Gy) of C57BL6/J mice and the occurrence of infectious and thrombotic complications in comparison with a bone marrow graft or prophylactic antibiotic treatment. Administration of 0.3 microg thrombopoietin, 2 hours after irradiation, protected 62% of the mice as opposed to no survival in placebo controls. A graft with a supraoptimal number of syngeneic bone marrow cells (10(6) cells) fully prevented mortality, whereas antibiotic treatment was ineffective. Blood cell recovery was observed in the thrombopoietin-treated mice but not in the placebo or antibiotic-treated group. Bone marrow and spleen cellularity as well as colony-forming unit granulocyte-macrophage and burst-forming unit erythroid were considerably increased in thrombopoietin-treated mice relative to controls. Histologic examination at day 11 revealed numerous petechiae and vascular obstructions within the brain microvasculature of placebo-treated mice, which was correlated with hypercoagulation and hypofibrinolysis. Thrombopoietin treatment prevented coagulation/fibrinolysis disorder and vascular thrombosis. High fibrinogen levels were related to bacterial infections in 67% of placebo-treated mice and predicted mortality, whereas the majority of the thrombopoietin-treated mice did not show high fibrinogen levels and endotoxin was not detectable in plasma. We conclude that thrombopoietin administration prevents mortality in mice subjected to 9-Gy total body irradiation both by interfering in the cascade leading to thrombotic complications and by amelioration of neutrophil and platelet recovery and thus protects against infections and hemorrhages.lld:pubmed
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pubmed-article:11164103pubmed:dateRevised2009-11-3lld:pubmed
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pubmed-article:11164103pubmed:year2001lld:pubmed
pubmed-article:11164103pubmed:articleTitleSingle administration of thrombopoietin to lethally irradiated mice prevents infectious and thrombotic events leading to mortality.lld:pubmed
pubmed-article:11164103pubmed:affiliationInstitut de Protection et de Sûreté Nucléaire, IPSN, Fontenay-aux-Roses Cedex, France. marc-andre.mouthon@ipsn.frlld:pubmed
pubmed-article:11164103pubmed:publicationTypeJournal Articlelld:pubmed
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