Research and Development, Australian Red Cross Lifeblood, Brisbane, QLD, Australia.
School of Medicine, University of Queensland, Brisbane, QLD, Australia.
J Cell Mol Med. 2020 Apr;24(8):4791-4803. doi: 10.1111/jcmm.15154. Epub 2020 Mar 17.
Coronary artery bypass grafting (CABG) triggers a systemic inflammatory response that may contribute to adverse outcomes. Dendritic cells (DC) and monocytes are immunoregulatory cells potentially affected by CABG, contributing to an altered immune state. This study investigated changes in DC and monocyte responses in CABG patients at 5 time-points: admission, peri-operative, ICU, day 3 and day 5. Whole blood from 49 CABG patients was used in an ex vivo whole blood culture model to prospectively assess DC and monocyte responses. Lipopolysaccharide (LPS) was added in parallel to model responses to an infectious complication. Co-stimulatory and adhesion molecule expression and intracellular mediator production was measured by flow cytometry. CABG modulated monocyte and DC responses. In addition, DC and monocytes were immunoparalysed, evidenced by failure of co-stimulatory and adhesion molecules (eg HLA-DR), and intracellular mediators (eg IL-6) to respond to LPS stimulation. DC and monocyte modulation was associated with prolonged ICU length of stay and post-operative atrial fibrillation. DC and monocyte cytokine production did not recover by day 5 post-surgery. This study provides evidence that CABG modulates DC and monocyte responses. Using an ex vivo model to assess immune competency of CABG patients may help identify biomarkers to predict adverse outcomes.
冠状动脉旁路移植术 (CABG) 会引发全身性炎症反应,可能导致不良后果。树突状细胞 (DC) 和单核细胞是受 CABG 影响的免疫调节细胞,有助于改变免疫状态。本研究在 5 个时间点:入院时、围手术期、ICU、第 3 天和第 5 天,检测了 CABG 患者的 DC 和单核细胞反应变化。使用体外全血培养模型对 49 名 CABG 患者的全血进行前瞻性评估,以评估 DC 和单核细胞反应。同时添加脂多糖 (LPS) 以模拟对感染并发症的反应。通过流式细胞术测量共刺激和粘附分子表达以及细胞内介质产生。CABG 调节单核细胞和 DC 反应。此外,DC 和单核细胞被免疫麻痹,这表现为共刺激和粘附分子(例如 HLA-DR)以及细胞内介质(例如 IL-6)对 LPS 刺激无反应。DC 和单核细胞的调节与 ICU 住院时间延长和术后心房颤动有关。术后第 5 天,DC 和单核细胞细胞因子的产生仍未恢复。本研究提供了 CABG 调节 DC 和单核细胞反应的证据。使用体外模型评估 CABG 患者的免疫功能可能有助于识别预测不良后果的生物标志物。