An elevated concentration of fibrinogen in blood is a significant risk factor during many pathological diseases, as it leads to an increase in red blood cells (RBC) aggregation, resulting in hemorheological disorders. Despite the biomedical importance, the mechanisms of fibrinogen-induced RBC aggregation are still debatable. One of the discussed models is the non-specific adsorption of fibrinogen macromolecules onto the RBC membrane, leading to the cells bridging in aggregates. However, recent works point to the specific character of the interaction between fibrinogen and the RBC membrane. Fibrinogen is the major physiological ligand of glycoproteins receptors IIbIIIa (GPIIbIIIa or αIIββ3 or CD41/CD61). Inhibitors of GPIIbIIIa are widely used in clinics for the treatment of various cardiovascular diseases as antiplatelets agents preventing the platelets’ aggregation. However, the effects of GPIIbIIIa inhibition on RBC aggregation are not sufficiently well studied. The objective of the present work was the complex multimodal in vitro study of the interaction between fibrinogen and the RBC membrane, revealing the role of GPIIbIIIa in the specificity of binding of fibrinogen by the RBC membrane and its involvement in the cells’ aggregation process. We demonstrate that GPIIbIIIa inhibition leads to a significant decrease in the adsorption of fibrinogen macromolecules onto the membrane, resulting in the reduction of RBC aggregation. We show that the mechanisms underlying these effects are governed by a decrease in the bridging components of RBC aggregation forces.

中文翻译：

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激光凝集法，流式细胞术和光镊结合微流控技术评估纤维蛋白原大分子与红细胞膜的相互作用

血液中纤维蛋白原的浓度升高是许多病理疾病中的重要危险因素，因为它会导致红细胞（RBC）聚集增加，从而导致血液流变学异常。尽管具有生物医学重要性，但纤维蛋白原诱导的RBC聚集的机制仍存在争议。讨论的模型之一是纤维蛋白原大分子在RBC膜上的非特异性吸附，导致细胞聚集在聚集物中。但是，最近的研究指出了纤维蛋白原与RBC膜之间相互作用的特殊特征。纤维蛋白原是糖蛋白受体IIbIIIa（GPIIbIIIa或αIIββ3或CD41 / CD61）的主要生理配体。GPIIbIIIa抑制剂作为防止血小板聚集的抗血小板药，在临床上广泛用于治疗各种心血管疾病。但是，GPIIbIIIa抑制对RBC聚集的影响尚未得到充分研究。本研究的目的是对纤维蛋白原与RBC膜之间的相互作用进行复杂的多模式体外研究，揭示GPIIbIIIa在RBC膜与纤维蛋白原结合的特异性及其在细胞聚集过程中的作用。我们证明GPIIbIIIa抑制导致纤维蛋白原大分子在膜上的吸附显着减少，从而导致RBC聚集减少。