Ongoing exposure to peritoneal dialysis fluid alters resident peritoneal macrophage phenotype and activation propensity
Ongoing exposure to peritoneal dialysis fluid alters resident peritoneal macrophage phenotype and activation propensity
复制标题
持续暴露于腹膜透析液会改变腹膜巨噬细胞的表型和激活倾向
DOI：
10.1101/2020.03.02.973404
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Sutherland T
中科院分区：
文献类型：
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作者：
Sutherland T
腹膜透析（PD）是慢性肾病患者血液透析的一种更连续的替代方案，在生存、患者独立性和医疗保健成本方面具有相当大的初始获益。然而，长期PD与显著病理学相关，否定了血液透析的积极作用。重要的是，腹膜炎和巨噬细胞活化与疾病进展和治疗失败密切相关。然而，巨噬细胞生物学的最新进展表明不同细胞来源的巨噬细胞具有相反的功能。虽然单核细胞衍生的巨噬细胞在一些纤维化模型中促进疾病进展，但组织驻留巨噬细胞与保护作用相关。因此，我们旨在确定组织驻留巨噬细胞对小鼠中PD诱导的炎症的相对贡献。出乎意料的是，我们发现腹膜驻留巨噬细胞的稳态特征、抗炎和巨噬细胞功能的逐渐丧失，伴随着对外部刺激的增强的炎症反应。此外，透析液中葡萄糖降解产物的存在导致炎症明显增强，组织驻留细胞几乎完全消失。因此，组织驻留巨噬细胞的改变可能使长期PD患者对腹膜炎敏感，从而导致纤维化/硬化。
Peritoneal dialysis (PD) is a more continuous alternative to haemodialysis, for patients with chronic kidney disease, with considerable initial benefits for survival, patient independence and healthcare costs. However, long-term PD is associated with significant pathology, negating the positive effects over haemodialysis. Importantly, peritonitis and activation of macrophages is closely associated with disease progression and treatment failure. However, recent advances in macrophage biology suggest opposite functions for macrophages of different cellular origins. While monocyte-derived macrophages promote disease progression in some models of fibrosis, tissue resident macrophages have rather been associated with protective roles. Thus, we aimed to identify the relative contribution of tissue resident macrophages to PD induced inflammation in mice. Unexpectedly, we found an incremental loss of homeostatic characteristics, anti-inflammatory and efferocytic functionality in peritoneal resident macrophages, accompanied by enhanced inflammatory responses to external stimuli. Moreover, presence of glucose degradation products within the dialysis fluid led to markedly enhanced inflammation and almost complete disappearance of tissue resident cells. Thus, alterations in tissue resident macrophages may render long-term PD patients sensitive to developing peritonitis and consequently fibrosis/sclerosis.