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

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

doi:10.1159/000443784

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

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

Authors

Natalia Borges Bonan¹, Thiago M Steiner, Viktoriya Kuntsevich, Grazia Maria Virzì, Marina Azevedo, Lia Sumie Nakao, Fellype Carvalho Barreto, Claudio Ronco, Stephan Thijssen, Peter Kotanko, Roberto Pecoits-Filho, Andréa N Moreno-Amaral

Affiliation

¹ Pontifx00ED;cia Universidade Catx00F3;lica do Paranx00E1;, Curitiba, Brazil.

PMID: 26848873
DOI: 10.1159/000443784

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcysteine / pharmacology
Adolescent
Adult
Aged
Aged, 80 and over
Anemia / blood
Anemia / immunology*
Anemia / pathology
Case-Control Studies
Coculture Techniques
Eryptosis / drug effects
Eryptosis / immunology*
Erythrocytes / drug effects
Erythrocytes / immunology*
Erythrocytes / pathology
Female
Free Radical Scavengers / pharmacology
GPI-Linked Proteins / genetics
GPI-Linked Proteins / immunology
Gene Expression Regulation
Humans
Immune Sera / pharmacology
Lipopolysaccharide Receptors / genetics
Lipopolysaccharide Receptors / immunology
Male
Middle Aged
Monocytes / drug effects
Monocytes / immunology*
Monocytes / pathology
Phagocytosis / drug effects
Primary Cell Culture
Reactive Oxygen Species / antagonists & inhibitors
Reactive Oxygen Species / metabolism
Receptors, IgG / genetics
Receptors, IgG / immunology
Renal Dialysis
Renal Insufficiency, Chronic / blood
Renal Insufficiency, Chronic / immunology
Renal Insufficiency, Chronic / pathology
Renal Insufficiency, Chronic / therapy*
Uremia / blood
Uremia / immunology*
Uremia / pathology

Substances

FCGR3B protein, human
Free Radical Scavengers
GPI-Linked Proteins
Immune Sera
Lipopolysaccharide Receptors
Reactive Oxygen Species
Receptors, IgG
Acetylcysteine