In sickle cell anemia, deoxygenation causes erythrocytes to distort, while reoxygenation permits them to recover a normal biconcave disk shape. Irreversibly sickled cells (ISCs) remain distorted when reoxygenated and have been thought to have among the highest intracellular hemoglobin concentrations of the sickle red cell population and therefore the greatest vulnerability to vasoocclusion. Using a new optical method, which we describe, we have made precise measurements of the intracellular hemoglobin concentration, and intracellular O2 saturation, of ISCs, as well as oxygenated sickle cells with a normal biconcave disc shape, and cells with shapes distorted by the sickle fibers they contain. This method also provides good estimates of cell volumes, and hemoglobin per red cell. The concentration distribution of the ISCs is found to be similar to normal, discoid cells. Average ISC volumes exceed their discoid counterparts, with a much broader distribution, arguing against dehydration as their origin. The concentration distribution of the polymer-laden sickled cells is significantly higher in mean value, and their volume distributions indicate some dehydration. Previous assumptions about ISCs may have thus been colored by the presence of sickle cells that did contain polymer, and true ISCs may be much more benign than once thought, which underscores the importance of accurate measurement on individual cells. This method could be used to follow changes in individual cell properties under various specific perturbations, and where characterization by flow cytometry is infeasible.

中文翻译：

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新的单细胞测量表明，不可逆的镰状细胞既不致密也不脱水


在镰状细胞贫血中，脱氧导致红细胞扭曲，而再氧合使它们能够恢复正常的双凹盘形状。不可逆的镰状细胞 （ISC） 在再氧合时保持扭曲，并且被认为具有镰状红细胞群中最高的细胞内血红蛋白浓度，因此最容易受到血管闭塞的影响。使用我们描述的一种新的光学方法，我们对 ISC 的细胞内血红蛋白浓度和细胞内 O 2 饱和度进行了精确测量，以及具有正常双凹盘形状的含氧镰状细胞，以及形状因它们所含的镰状纤维而变形的细胞。该方法还可以很好地估计细胞体积和每个红细胞的血红蛋白。发现 ISC 的浓度分布与正常的盘状细胞相似。平均 ISC 体积超过其盘状体积，分布范围更广，反对脱水是其根源。载有聚合物的镰状细胞的浓度分布的平均值显著较高，其体积分布表明存在一定程度的脱水。因此，以前关于 ISC 的假设可能受到确实含有聚合物的镰状细胞的存在的影响，而真正的 ISC 可能比以前认为的要良性得多，这强调了准确测量单个细胞的重要性。该方法可用于跟踪在各种特定扰动下单个细胞特性的变化，以及通过流式细胞术进行表征不可行的情况。