Papadopoulos Charalampos, Spourita Eleftheria, Mimidis Konstantinos, Kolios George, Tentes Loannis, Anagnostopoulos Konstantinos
Laboratory of Biochemistry, Department of Basic Sciences, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
First Department of Internal Medicine, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Metab Syndr Relat Disord. 2022 Sep;20(7):377-383. doi: 10.1089/met.2022.0006. Epub 2022 May 9.
Nonalcoholic fatty liver disease (NAFLD) constitutes a significant cause of deaths, liver transplantations, and economic costs worldwide. Despite extended research, investigations on the role of erythrocytes are scarce. Red blood cells from experimental animals and human patients with NAFLD present phosphatidylserine exposure, which is then recognized by Kupffer cells. This event leads to erythrophagocytosis and amplification of inflammation through iron disposition. In addition, it has been shown that erythrocytes from NAFLD patients release the chemokine monocyte chemoattractant protein-1 (MCP1), leading to increased tumor necrosis factor alpha release from macrophages RAW 264.7. However, erythrophagocytosis can also be caused by reduced CD47 levels. Moreover, increased MCP1 release could be either signal-induced or caused by higher MCP1 levels on the erythrocyte membrane. Finally, erythrocyte efferocytosis could provide additional inflammatory metabolites. In this study, we measured the erythrocyte membrane levels of CD47 and MCP1 by enzyme-linked immunosorbent assay, and cholesterol and sphingosine with thin-layer chromatography. Eighteen patients (8 men and 10 women, aged 56.7 ± 11.5 years) and 14 healthy controls (7 men and 7 women, aged 39.3 ± 15.6 years) participated in our study. The erythrocyte CD47 levels were decreased in the erythrocyte membranes of NAFLD patients (844 ± 409 pg/mL) compared with healthy controls (2969 ± 1936 pg/mL) with = 0.012. Levels of MCP1 increased in NAFLD patients (389 ± 255 pg/mL) compared with healthy controls (230 ± 117 pg/mL) with = 0.0274, but low statistical power. Moreover, in erythrocyte membranes, there was a statistically significant accumulation of sphingosine and cholesterol in NAFLD patients compared with healthy controls. Our results imply that erythrocytes release chemotactic "find me" signals (MCP1) while containing reduced "do not eat me" signals (CD47). These molecules can lead to erythrophagocytosis. Next, increased "goodbye" signals (sphingosine and cholesterol) could augment inflammation by metabolic reprogramming.
非酒精性脂肪性肝病（NAFLD）是全球范围内导致死亡、肝移植及产生经济成本的一个重要原因。尽管已有广泛研究，但对红细胞作用的调查却很匮乏。来自实验动物和患有NAFLD的人类患者的红细胞呈现出磷脂酰丝氨酸暴露，随后被库普弗细胞识别。这一事件会导致红细胞吞噬作用，并通过铁的沉积使炎症放大。此外，研究表明，NAFLD患者的红细胞会释放趋化因子单核细胞趋化蛋白-1（MCP1），导致巨噬细胞RAW 264.7释放更多肿瘤坏死因子α。然而，红细胞吞噬作用也可能由CD47水平降低引起。此外，MCP1释放增加可能是信号诱导的，也可能是由于红细胞膜上MCP1水平升高所致。最后，红细胞胞葬作用可能会产生额外的炎症代谢产物。在本研究中，我们通过酶联免疫吸附测定法测量了CD47和MCP1的红细胞膜水平，并用薄层色谱法测量了胆固醇和鞘氨醇水平。18名患者（8名男性和10名女性，年龄56.7±11.5岁）和14名健康对照者（7名男性和7名女性，年龄39.3±15.6岁）参与了我们的研究。与健康对照者（2969±1936 pg/mL）相比，NAFLD患者红细胞膜中的红细胞CD47水平降低（844±409 pg/mL），P = 0.012。与健康对照者（230±117 pg/mL）相比，NAFLD患者的MCP1水平升高（389±255 pg/mL），P = 0.0274，但统计效力较低。此外，与健康对照者相比，NAFLD患者红细胞膜中的鞘氨醇和胆固醇有统计学意义的积累。我们的结果表明，红细胞在释放趋化性“找到我”信号（MCP1）的同时，所含的“别吃我”信号（CD47）减少。这些分子可导致红细胞吞噬作用。接下来，增加的“再见”信号（鞘氨醇和胆固醇）可通过代谢重编程增强炎症反应。
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