In vivo volume and hemoglobin dynamics of human red blood cells.
In vivo volume and hemoglobin dynamics of human red blood cells.
复制标题
DOI：
10.1371/journal.pcbi.1003839
复制
发表时间：
2014-10
影响因子：
4.3
通讯作者：
Higgins JM
中科院分区：
文献类型：
--
作者：
Malka R;Delgado FF;Manalis SR;Higgins JM
人红细胞（rbc）在血液中的寿命约100天内会损失约30%的体积和约20%的血红蛋白（Hb）含量。这些观察结果有充分的文献记载，但这些体积和血红蛋白损失事件的机制尚不清楚。红细胞在循环过程中脱落含血红蛋白的囊泡，这一过程被认为是红细胞成熟过程中物理特性变化的主导因素。我们将理论与单细胞测量相结合，研究囊泡对体积、Hb质量和膜的减少的影响。我们表明，囊泡脱落本身足以解释膜损失，而不是体积或Hb损失。我们使用人红细胞的干质量测量来验证模型，并提出额外的未知机制控制体积和Hb减少，并负责观察到的减少的约90%。红细胞种群特征在临床中用于监测和诊断各种疾病，包括营养不良、炎症和癌症。细胞成熟过程的定量表征可能有助于早期发现成熟模式改变的临床条件。红细胞浓度（RBC）、平均体积（MCV）和血红蛋白含量（MCH）是全血细胞计数的常规测量，全血细胞计数是大多数疾病筛查、诊断和管理的基本临床测试。MCV和MCH的变异与许多重要的临床疾病有关，但我们不了解控制这些红细胞物理特征的机制。囊泡脱落被认为是最重要的，但我们在这里表明，囊泡脱落的主导作用违反了经验几何和生物物理约束。一个额外的未知过程必须承担主要责任。我们表明，这一重要的未知过程必须耦合到RBC表面积的变化，我们量化其影响的幅度。
Human red blood cells (RBCs) lose ∼30% of their volume and ∼20% of their hemoglobin (Hb) content during their ∼100-day lifespan in the bloodstream. These observations are well-documented, but the mechanisms for these volume and hemoglobin loss events are not clear. RBCs shed hemoglobin-containing vesicles during their life in the circulation, and this process is thought to dominate the changes in the RBC physical characteristics occurring during maturation. We combine theory with single-cell measurements to investigate the impact of vesiculation on the reduction in volume, Hb mass, and membrane. We show that vesicle shedding alone is sufficient to explain membrane losses but not volume or Hb losses. We use dry mass measurements of human RBCs to validate the models and to propose that additional unknown mechanisms control volume and Hb reduction and are responsible for ∼90% of the observed reduction. RBC population characteristics are used in the clinic to monitor and diagnose a wide range of conditions including malnutrition, inflammation, and cancer. Quantitative characterization of cellular maturation processes may help in the early detection of clinical conditions where maturation patterns are altered. Red blood cell concentration (RBC), mean volume (MCV), and hemoglobin content (MCH) are routinely measured in the complete blood count, a fundamental clinical test essential for the screening, diagnosis, and management of most diseases. Variation in MCV and MCH is associated with many important clinical conditions, but we do not understand the mechanisms controlling these red blood cell physical characteristics. Vesicle shedding is thought to be most important, but we show here that a dominant role for vesicle shedding violates empirical geometric and biophysical constraints. An additional unknown process must be primarily responsible. We show that this important unknown process must be coupled to changes in RBC surface area, and we quantify the magnitude of its effects.
登录
查看更多内容
影响因子：
3.4
作者：
Pattanapanyasat, K;Noulsri, E;Webster, HK
通讯作者：
Webster, HK
影响因子：
2.9
作者：
DUMASWALA, UJ;GREENWALT, TJ
通讯作者：
GREENWALT, TJ
影响因子：
8.6
作者：
Phillips KG;Jacques SL;McCarty OJ
通讯作者：
McCarty OJ
DOI：
10.1073/pnas.1012747107
发表时间：
2010-11-23
影响因子：
11.1
作者：
Higgins, John M.;Mahadevan, L.
通讯作者：
Mahadevan, L.
影响因子：
20.3
作者：
DONOFRIO, G;CHIRILLO, R;MICCIULLI, G
通讯作者：
MICCIULLI, G