García-González Victor, Gutiérrez-Quintanar Nadia, Mas-Oliva Jaime
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. 04510 México, D.F. México.
Facultad de Medicina, Universidad Autónoma de Baja California, Mexicali, 21000 Baja California, México.
Sci Rep. 2015 Nov 5;5:16091. doi: 10.1038/srep16091.
Described by our group a few years ago, the cholesteryl-ester transfer protein isoform (CETPI), exclusively expressed in the small intestine and present in human plasma, lacked a functional identification for a role of physiological relevance. Now, this study introduces CETPI as a new protein with the potential capability to recognise, bind and neutralise lipopolysaccharides (LPS). Peptides derived from the C-terminal domain of CETPI showed that CETPI not only might interact with several LPS serotypes but also might displace LPS bound to the surface of cells. Peptide VSAK, derived from the last 18 residues of CETPI, protected against the cytotoxic effect of LPS on macrophages. At high concentrations, when different cell types were tested in culture, it did not exhibit cytotoxicity by itself and it did prevent the expression of pro-inflammatory cytokines as well as the generation of oxidative stress conditions. In a rabbit model of septic shock, the infusion of peptide VSAK exerted a protective effect against the effects of LPS and reduced the presence of tumor necrosis factor-alpha (TNFα) in plasma. Therefore, CETPI is proposed as a new protein with the capability to advance the possibilities for better understanding and treatment of the dangerous effects of LPS in vivo.
几年前我们团队描述过，胆固醇酯转运蛋白异构体（CETPI）仅在小肠中表达且存在于人体血浆中，此前缺乏对其生理相关作用的功能鉴定。现在，这项研究表明CETPI是一种新蛋白，具有识别、结合和中和脂多糖（LPS）的潜在能力。源自CETPI C末端结构域的肽段显示，CETPI不仅可能与多种LPS血清型相互作用，还可能取代结合在细胞表面的LPS。源自CETPI最后18个残基的肽段VSAK可保护巨噬细胞免受LPS的细胞毒性作用。在高浓度下，当在培养中测试不同细胞类型时，它本身不表现出细胞毒性，并且确实能阻止促炎细胞因子的表达以及氧化应激条件的产生。在脓毒症休克的兔模型中，输注肽段VSAK对LPS的作用具有保护作用，并降低了血浆中肿瘤坏死因子-α（TNFα）的水平。因此，CETPI被认为是一种新蛋白，有能力提升更好地理解和治疗LPS在体内危险作用可能性。
