University of Ulm, ZBMT, Department of Biomaterials, Ulm, Germany.
Clin Hemorheol Microcirc. 2013 Jan 1;54(3):273-85. doi: 10.3233/CH-131733.
Red blood cells demonstrate a unique ability for repeated large deformation. Under the influence of a variety of agents, shapes other than the discocyte--e.g. stomatocytes or echinocytes--can be observed. Some radiographic agents induce shape changes from discocytic to echinocytic cells. Especially the echinocyte formation is associated with a rigidification of the cells bearing the risk of a hindered capillary passage of the echinocytes. The mechanisms leading to the formation of echinocytes are not well understood assuming that the membrane cytoskeleton is a key player. That is why this examination was focused on the participation of components of the membrane cytoskeleton in the formation of echinocytes and the protrusions accompanying the formation of echinocytes. Two radiographic contrast media approved for intra-arterial application were used to study echinocyte formation (Iodixanol320; Iopromide370). In the in vitro study serious changes in the membrane cytoskeleton were only found in those erythrocytes incubated in plasma supplemented with Iopromide370 (30%v/v). The shape of the spectrin net was completely altered; from the more homogeneous distribution--typical of cells in autologous plasma and also of cells in plasma supplemented with Iodixanol320--to a distribution of spectrin concentrated in the membrane-near regions with the appearance of spectrin-actin co-localization. Co-localized spectrin with actin was also found around the membranous roots of protrusions which resemble exocytotic processes. In central parts of the cells there was a pronounced dissociation of spectrin and actin; green coloured condensed spectrin bundles originating from the cell membrane reached up to the root of the protrusions. Separate from this there were also fine long actin fibres passing through the whole cell. The incubation of erythrocytes in plasma supplemented with Iopromide370 induced rounded bubble-like protrusions from the cell membrane containing almost completely long bundles of actin fibres. The examination confirmed earlier studies showing that some radiographic contrast media are able to induce echinocyte formation. Furthermore, subcellular mechanisms were revealed explaining the different effects of Iodixanol in comparison to Iopromide.
红细胞表现出独特的多次大幅变形能力。在各种药剂的影响下，除圆盘形细胞以外的形状——例如棘形细胞或刺形细胞——也能观察到。一些射线造影剂可诱导细胞从圆盘形变为棘形。尤其是棘形细胞的形成与细胞僵硬有关，而这些僵硬的细胞可能会阻碍棘形细胞通过毛细血管。导致棘形细胞形成的机制尚不清楚，但假设膜细胞骨架是关键因素。这就是为什么这项检查专注于膜细胞骨架的成分在棘形细胞形成以及伴随棘形细胞形成的突起中的参与。两种已批准用于动脉内应用的射线造影剂被用于研究棘形细胞形成（碘海醇 320；碘普罗胺 370）。在体外研究中，只有在含有碘普罗胺 370（30%v/v）的血浆中孵育的红细胞中才发现严重的膜细胞骨架变化。血影蛋白网的形状完全改变；从更均匀的分布（自体血浆中的细胞以及含有碘海醇 320 的血浆中的细胞的典型分布）到血影蛋白在靠近细胞膜的区域集中的分布，出现血影蛋白-肌动蛋白共定位。也在类似于胞吐过程的突起的膜根部周围发现与肌动蛋白共定位的血影蛋白。在细胞的中心部分，血影蛋白和肌动蛋白明显分离；从细胞膜发出的绿色浓缩血影蛋白束一直延伸到突起的根部。除此之外，还有细而长的肌动蛋白纤维穿过整个细胞。在含有碘普罗胺 370 的血浆中孵育红细胞会从细胞膜上诱导出圆形气泡状突起，其中几乎完全包含长束的肌动蛋白纤维。该检查证实了早期的研究结果，表明一些射线造影剂能够诱导棘形细胞形成。此外，还揭示了亚细胞机制，解释了碘海醇与碘普罗胺的不同作用。
