Severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes
Severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes
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DOI：
10.1182/blood-2005-08-3460
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发表时间：
2006-02-01
期刊：
影响因子：
20.3
通讯作者：
Schofield, L
中科院分区：
文献类型：
--
作者：
Evans, KJ;Hansen, DS;Schofield, L
严重疟疾贫血（SMA）是最常见的危及生命的疟疾并发症，可能是全球大部分疟疾死亡的原因。为了探索发病机制，我们开发了一种新型 SMA 小鼠模型，其中寄生虫血症在循环红细胞 (RBC) 的 1.0% 左右达到峰值，但血红蛋白水平下降至基线的 47% 至 56%。贫血的严重程度与寄生虫血症的峰值水平或累积水平无关，但与明显感染的持续时间有动力学相关。对循环血液区室的体内生物素化分析表明，贫血是由红细胞周转加速引起的。标记后 8 天，标记的红细胞减少至循环细胞的 1%，表明整个血室在大约一周内已被更新。在 SMA 动物中，新输注的红细胞的存活率也显着降低，但当将 SMA 供体的红细胞转移到初始接受者体内时，存活率并没有改变，这表明针对目标红细胞的功能修改很少。吞噬细胞或CD4(+) T淋巴细胞的消耗可显着减轻贫血。这项研究表明，免疫机制可能通过促进未感染红细胞的加速更新来促进 SMA。
Severe malarial anemia (SMA) is the most frequent life-threatening complication of malaria and may contribute to the majority of malarial deaths worldwide. To explore the mechanisms of pathogenesis, we developed a novel murine model of SMA in which parasitemias peaked around 1.0% of circulating red blood cells (RBCs) and yet hemoglobin levels fell to 47% to 56% of baseline. The severity of anemia was independent of the level of peak or cumulative parasitemia, but was linked kinetically to the duration of patent infection. In vivo biotinylation analysis of the circulating blood compartment revealed that anemia arose from accelerated RBC turnover. Labeled RBCs were reduced to 1% of circulating cells by 8 days after labeling, indicating that the entire blood compartment had been turned over in approximately one week. The survival rate of freshly transfused RBCs was also markedly reduced in SMA animals, but was not altered when RBCs from SMA donors were transferred into naive recipients, suggesting few functional modifications to target RBCs. Anemia was significantly alleviated by depletion of either phagocytic cells or CD4(+) T lymphocytes. This study demonstrates that immunologic mechanisms may contribute to SMA by promoting the accelerated turnover of uninfected RBCs.