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TXAS-deleted mice exhibit normal thrombopoiesis, defective hemostasis, and resistance to arachidonate-induced death
- Source :
- Blood; July 2004, Vol. 104 Issue: 1 p135-142, 8p
- Publication Year :
- 2004
-
Abstract
- Besides its well-recognized role in hemostasis and thrombosis, thromboxane A2synthase (TXAS) is proposed to be involved in thrombopoiesis and lymphocyte differentiation. To evaluate its various physiologic roles, we generated TXAS-deleted mice by gene targeting. TXAS–/–mice had normal bone marrow megakaryocytes, normal blood platelet counts, and normal CD4 and CD8 lymphocyte counts in thymus and spleen. Platelets from TXAS–/–mice failed to aggregate or generate thromboxane B2in response to arachidonic acid (AA) but produced increased prostaglandin-E2(PGE2), PGD2, and PGF2α. AA infusion caused a progressive drop of mean arterial pressure (MAP), cardiac arrest, and death in wild-type (WT) mice but did not induce shock in TXAS–/–mice or in WT and TXAS–/–mice treated with antagonist to the thromboxane-prostanoid (TP) receptor. The TXAS–/–mice were able to maintain normal MAP upon AA insult when TP was present but were unable to do so when TP was blocked by an antagonist, suggesting a role of endoperoxide accumulation in influencing MAP. We conclude that TXAS is not essential for thrombopoiesis and lymphocyte differentiation. Its deficiency causes a mild hemostatic defect and protects mice against arachidonate-induced shock and death. The TXAS-deleted mice will be valuable for investigating the roles of arachidonate metabolic shunt in various pathophysiologic processes.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 104
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs56979947
- Full Text :
- https://doi.org/10.1182/blood-2003-10-3661