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首页> 外文期刊>British Journal of Haematology >Thrombopoietic effect of VPAC1 inhibition during megakaryopoiesis
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Thrombopoietic effect of VPAC1 inhibition during megakaryopoiesis

机译：巨核细胞生成过程中VPAC1抑制的血小板生成作用

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SummaryMegakaryocytes and platelets express the stimulatory G protein (Gs)-coupled VPAC1 receptor, for which the pituitary adenylyl cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are agonists. The neuropeptide PACAP and VPAC1 were previously found to negatively regulate megakaryopoiesis, and inhibition of their physiological pathway was found to have a thrombopoietic effect in conditions where megakaryo-poiesis and thrombopoiesis were impaired, such as chemotherapy-induced thrombocytopenia and congenital thrombocytopenia. The present study explored the thrombopoietic effect of VPAC1 inhibition in a murine model of syngeneic bone marrow transplantation (BMT) and in passive immune thrombocytopenia. Treatment of donor mice with a neutralizing anti-VPAC1 antibody stimulated the initial, most critical recovery of the platelets in irradiated mice. In the passive immune thrombocytopenia model, we observed a thrombopoietic effect, resulting in a less severe platelet drop after induction of their removal in the spleen by an anti-platelet antibody. We concluded that inhibition of the physiological PACAP/VPAC1 pathway could stimulate in vivo megakaryopoiesis. This inhibition can be applied to attenuate thrombocytopenia in conditions where platelets are destroyed as the major pathogenetic mechanism, e.g. immune thrombocytopenia purpura, or need to be produced de novo, e.g. after irradiation and BMT.
机译：小结真核细胞和血小板表达刺激性G蛋白（Gs）偶联的VPAC1受体，垂体腺苷酸环化酶激活肽（PACAP）和血管活性肠肽（VIP）是激动剂。先前发现神经肽PACAP和VPAC1负调节巨核细胞生成，发现其生理途径受到抑制，在巨核细胞生成和血小板生成受损的情况下，如化疗诱导的血小板减少和先天性血小板减少症，具有血小板生成作用。本研究探讨了VPAC1抑制在同基因骨髓移植（BMT）小鼠模型和被动免疫性血小板减少症中的血小板生成作用。用中和性抗VPAC1抗体治疗供体小鼠会刺激受辐照的小鼠的血小板最初，最关键的恢复。在被动免疫性血小板减少症模型中，我们观察到了血小板生成作用，通过抗血小板抗体诱导其在脾脏中的清除后，血小板的滴落程度降低了。我们得出的结论是，抑制生理性PACAP / VPAC1途径可以刺激体内巨核细胞生成。这种抑制作用可用于在血小板被破坏为主要致病机理的条件下，例如血小板减少，减轻血小板减少。免疫性血小板减少性紫癜，或需要重新产生，例如照射和BMT之后。

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