Patry Christian, Stamm Daniela, Betzen Christian, Tönshoff Burkhard, Yard Benito A, Beck Grietje Ch, Rafat Neysan
1Department of Pediatrics I, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
2Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany.
J Inflamm (Lond). 2018 May 16;15:10. doi: 10.1186/s12950-018-0186-7. eCollection 2018.
Endothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival. In this study, we investigated, whether surface expression of chemokine receptors and other receptors important for EPC homing is upregulated by EPC from septic patients and if this is associated with clinical outcome.
Peripheral blood mononuclear cells from septic patients ( = 30), ICU control patients ( = 11) and healthy volunteers ( = 15) were isolated by Ficoll density gradient centrifugation. FACS-analysis was used to measure the expression of the CXC motif chemokine receptors (CXCR)-2 and - 4, the receptor for advanced glycation endproducts (RAGE) and the stem cell factor receptor c-Kit. Disease severity was assessed via the Simplified Acute Physiology Score (SAPS) II. The serum concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor (SDF)-1α and angiopoietin (Ang)-2 were determined with Enzyme linked Immunosorbent Assays.
EPC from septic patients expressed significantly more CXCR-4, c-Kit and RAGE compared to controls and were associated with survival-probability. Significantly higher serum concentrations of VEGF, SDF-1α and Ang-2 were found in septic patients. SDF-1α showed a significant association with survival.
Our data suggest that SDF-1α and CXCR-4 signaling could play a crucial role in EPC homing in the course of sepsis.
脓毒症患者体内内皮祖细胞(EPC)数量增加,且与生存率相关。在本研究中,我们调查了脓毒症患者的EPC是否会上调趋化因子受体和其他对EPC归巢重要的受体的表面表达,以及这是否与临床结局相关。
通过Ficoll密度梯度离心法分离脓毒症患者(n = 30)、重症监护病房对照患者(n = 11)和健康志愿者(n = 15)的外周血单核细胞。采用流式细胞术分析检测CXC基序趋化因子受体(CXCR)-2和-4、晚期糖基化终产物受体(RAGE)以及干细胞因子受体c-Kit的表达。通过简化急性生理学评分(SAPS)II评估疾病严重程度。采用酶联免疫吸附测定法测定血清血管内皮生长因子(VEGF)、基质细胞衍生因子(SDF)-1α和血管生成素(Ang)-2的浓度。
与对照组相比,脓毒症患者的EPC表达的CXCR-4、c-Kit和RAGE明显更多,且与生存概率相关。脓毒症患者血清中VEGF、SDF-1α和Ang-2的浓度明显更高。SDF-1α与生存率显著相关。
我们的数据表明,SDF-1α和CXCR-4信号传导可能在脓毒症过程中EPC归巢中起关键作用。