Domínguez Victoria, Govezensky Tzipe, Gevorkian Goar, Larralde Carlos
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México.
Haematologica. 2003 Jun;88(6):679-87.
The physiopathogenesis of hemorrhagic phenomena in patients with autoimmune thrombocytopenic purpura is associated with low platelet levels. In the present work the relation between thrombocytopenia and bleeding was examined. The possible participation of endothelial cells in bleeding was also investigated.
Immune thrombocytopenia and bleeding were studied in mice injected with anti-mouse and anti-human platelet polyclonal rabbit IgG. Platelet levels were measured at different times and bleeding signs were systematically recorded. ANOVA tests were used to compare platelet levels. Binding of anti-platelet antibodies to vascular endothelial cells was analyzed by immunohistochemistry.
Three different doses of anti-platelet IgG caused the same low platelet levels, but bleeding occurred only with high doses of anti-platelet IgG irrespective of the platelet levels. No inflammation around blood vessels was observed in paraffin-embedded tissue sections of organs. Immunohistochemistry demonstrated anti-platelet antibodies bound to vascular endothelium.
We showed lack of correlation between platelet counts and bleeding in a murine model. The binding of anti-platelet IgG to endothelial cells of small vessels is an indication that antibody-mediated endothelial activation, in addition to thrombocytopenia, could be participating in bleeding.
自身免疫性血小板减少性紫癜患者出血现象的病理生理机制与血小板水平降低有关。在本研究中,我们探讨了血小板减少与出血之间的关系,同时也研究了内皮细胞在出血过程中可能发挥的作用。
通过给小鼠注射抗小鼠和抗人血小板多克隆兔IgG来研究免疫性血小板减少和出血情况。在不同时间点测量血小板水平,并系统记录出血症状。采用方差分析检验来比较血小板水平。通过免疫组织化学分析抗血小板抗体与血管内皮细胞的结合情况。
三种不同剂量的抗血小板IgG均可导致相同程度的血小板水平降低,但只有高剂量的抗血小板IgG会引发出血,且与血小板水平无关。在器官的石蜡包埋组织切片中未观察到血管周围有炎症。免疫组织化学显示抗血小板抗体与血管内皮细胞结合。
我们在小鼠模型中发现血小板计数与出血之间缺乏相关性。抗血小板IgG与小血管内皮细胞的结合表明,除血小板减少外,抗体介导的内皮细胞激活可能也参与了出血过程。