尿毒症毒性诱导的红细胞凋亡和单核细胞调节：红细胞吞噬作用作为肾性贫血的新途径

Uremic Toxicity-Induced Eryptosis and Monocyte Modulation: The Erythrophagocytosis as a Novel Pathway to Renal Anemia.

作者信息

Bonan Natalia Borges, Steiner Thiago M, Kuntsevich Viktoriya, Virzì Grazia Maria, Azevedo Marina, Nakao Lia Sumie, Barreto Fellype Carvalho, Ronco Claudio, Thijssen Stephan, Kotanko Peter, Pecoits-Filho Roberto, Moreno-Amaral Andréa N

机构信息

Pontifx00ED;cia Universidade Catx00F3;lica do Paranx00E1;, Curitiba, Brazil.

出版信息

Blood Purif. 2016;41(4):317-23. doi: 10.1159/000443784. Epub 2016 Feb 6.

DOI:10.1159/000443784

PMID:26848873

Abstract

BACKGROUND

We tested the effect of uremia on red blood cell (RBC) eryptosis, CD14++/CD16+ monocytes and erythrophagocytosis.

DESIGN

RBC and monocytes from chronic kidney disease (CKD) stages 3/4 (P-CKD3/4) or hemodialysis (HD) patients and healthy controls (HCs) cells incubated with sera pools from patients with CKD stages 2/3 (S-CKD2/3) or 4/5 (S-CKD4/5) were evaluated to assess eryptosis, monocyte phenotypes and reactive oxygen species (ROS) by cytometer. Erythrophagocytosis was evaluated by subsequent co-incubation of preincubated HC-monocytes and autologous-RBC.

RESULTS

HC-eryptosis (1.3 ± 0.9%) was lower than in HD (4.3 ± 0.5%) and HC-RBC incubated with S-CKD4/5 (5.6 ± 1%). CD14++/CD16+ were augmented in P-CKD3/4 (34.6 ± 8%) and HC-monocytes incubated with S-CKD4/5 (26.4 ± 7%) than in HC (5.4 ± 1%). In these cells, ROS was increased (44.5 ± 9%; control 9.6 ± 2%) and inhibited by N-acetylcysteine (25 ± 13%). Erythrophagocytosis was increased in CD14++/CD16+ (60.8 ± 10%) than in CD14++/CD16- (15.5 ± 2%).

CONCLUSIONS

Sera pools from CKD patients increase eryptosis and promote a proinflammatory monocyte phenotype. Both processes increased erythrophagocytosis, thereby suggesting a novel pathway for renal anemia.

摘要

背景

我们测试了尿毒症对红细胞（RBC）凋亡、CD14++/CD16+单核细胞和红细胞吞噬作用的影响。

设计

将慢性肾脏病（CKD）3/4期（P-CKD3/4）或血液透析（HD）患者以及健康对照（HC）的红细胞和单核细胞与CKD 2/3期（S-CKD2/3）或4/5期（S-CKD4/5）患者的血清池一起孵育，通过细胞仪评估红细胞凋亡、单核细胞表型和活性氧（ROS）。通过预先孵育的HC-单核细胞与自体红细胞随后共同孵育来评估红细胞吞噬作用。

结果

HC-红细胞凋亡（1.3±0.9%）低于HD（4.3±0.5%）以及与S-CKD4/5孵育的HC-RBC（5.6±1%）。与HC（5.4±1%）相比，P-CKD3/4（34.6±8%）以及与S-CKD4/5孵育的HC-单核细胞中CD14++/CD16+增加。在这些细胞中，ROS增加（44.5±9%；对照组9.6±2%），并被N-乙酰半胱氨酸抑制（25±13%）。CD14++/CD16+中的红细胞吞噬作用（60.8±10%）高于CD14++/CD16-（15.5±2%）。