Anemia and impaired stress-induced erythropoiesis in aceruloplasminemic mice
Anemia and impaired stress-induced erythropoiesis in aceruloplasminemic mice
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DOI：
10.1016/j.bcmd.2004.07.003
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发表时间：
2004-11-01
影响因子：
2.3
通讯作者：
Fox, PL
中科院分区：
文献类型：
--
作者：
Cherukuri, S;Tripoulas, NA;Fox, PL
铜蓝蛋白是一种丰富的含铜血浆蛋白，在铁稳态中起重要作用。遗传性Cp缺乏症患者在肝脏和其他器官有铁沉积，与铁通量受损一致。在一些患者中报道的轻度贫血表明，在红细胞生成过程中，Cp可能在铁传递到红细胞前体中的作用。为了研究Cp的这种功能，我们测定了正常情况下和诱导红细胞生成应激后Cp缺陷小鼠的血液学参数。Cp-/-小鼠红细胞压积、红细胞血红蛋白、红细胞体积和血清铁均低于正常水平。cp（-/-）和cp +/+小鼠红细胞数量、周转率和网织红细胞计数相同。因此，Cp-/-有轻微的小细胞性、低色素贫血，与正常红细胞形成一致，但铁可用性有缺陷。Cp-/-和Cp+/+小鼠在苯肼诱导的溶血性贫血中表现出相同的血液学参数下降，但Cp-/-小鼠在消除应激后恢复缓慢。将纯化的人Cp或饱和铁转铁蛋白给予Cp-/-小鼠，可部分恢复网织红细胞中血红蛋白的形成。Cp-/-小鼠的轻度贫血和应激反应减弱可能反映了网状内皮系统和红细胞生成系统之间铁循环效率低下。我们的研究结果表明，Cp通过向红细胞组织提供足够的铁而在红细胞生成中发挥作用，并且在红细胞生成应激后对Cp的需求增加。(C) 2004爱思唯尔公司版权所有。
Ceruloplasmin (Cp) is an abundant, copper-containing plasma protein with an important role in iron homeostasis. Patients with hereditary Cp deficiency have iron deposits in liver and other organs, consistent with impaired iron flux. The mild anemia reported in some patients suggests a possible role for Cp in iron delivery to red cell precursors during erythropoiesis. To investigate this function of Cp, we determined the hematologic parameters in Cp-deficient mice under normal conditions and after erythropoiesis-inducing stress. Cp-/- mice have below normal hematocrit, red cell hemoglobin and volume, and serum iron. Red cell number and turnover and reticulocyte counts were identical in cp(-/-) and Cp+/+ mice. Thus, Cp-/- have mild microcytic, hypochromic anemia consistent with normal red cell formation but defective iron availability. Cp-/- and Cp+/+ mice subjected to phenylhydrazine-induced hemolytic anemia exhibited identical decreases in hematologic parameters, but Cp-/- mice showed diminished recovery after removal of the stress. Administration of purified human Cp or iron-saturated transferrin to Cp-/- mice partially restored hemoglobin formation in reticulocytes. The mild anemia in Cp-/- mice and the diminished response to stress may reflect inefficient recycling of iron between the reticuloendothelial and erythropoietic systems. Our findings suggest a role for Cp in erythropoiesis by providing sufficient iron to the erythroid tissue and that the requirement for Cp is raised after erythropoietic stress. (C) 2004 Elsevier Inc. All rights reserved.