TXAS-deleted mice exhibit normal thrombopoiesis, defective hemostasis, and resistance to arachidonate-induced death

I. Shing Yu, Shu Rung Lin, Chin Chin Huang, Hui Yu Tseng, Pei Hsing Huang, Guey Yueh Shi, Hua Lin Wu, Chi Lu Tang, Pao Hsien Chu, Lee Ho Wang, Kenneth K. Wu, Shu Wha Lin

研究成果: Article同行評審

41 引文 斯高帕斯(Scopus)

摘要

Besides its well-recognized role in hemostasis and thrombosis, thromboxane A2 synthase (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 B2 in response to arachidonic acid (AA) but produced increased prostaglandin-E 2 (PGE2), PGD2, and PGF. 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.

原文English
頁(從 - 到)135-142
頁數8
期刊Blood
104
發行號1
DOIs
出版狀態Published - 2004 七月 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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