Immune Dysfunction in Uremia—An Update
Abstract
:1. Magnitude of the Problem: Mortality in Uremia
2. Oxidative Stress and Inflammation
3. Priming of Immune Cells
4. Apoptosis
5. Metabolic Kidney Activities
5.1. Erythropoietin and Iron
5.2. Vitamin D, Calcium, Parathyroid Hormone and Fibroblast Growth Factor 23
5.3. Renin, Angiotensin
6. Uremic Toxins
Uremic toxin | Functional disturbance |
---|---|
LMW Solutes | |
Phenylacetic acid (PAA) | Macrophages: inducible nitric oxide synthase ↓ [106]; |
PMNLs: oxidative burst, phagocytosis and integrin expression ↑; apoptosis ↓ [49] | |
Dinucleoside polyphosphates | Leukocytes: oxidative burst ↑ [107]. |
Guanidino compounds | Monocytes/macrophages: pro- and anti-inflammatory [108,109,110] |
Indoxyl sulfate | Endothel: E-selectin ↑ [111] |
P-cresyl sulfate | Leukocytes: basal oxidative burst ↑ [112] |
Homocysteine (Hcy) | ICAM-1 ↑ [113]; damage of DNA [114] and proteins [115] |
Methylglyoxal (MGO) | PMNLs: apoptosis ↑ [116], oxidative burst ↑ [117]; |
Monocytes: apoptosis ↑ [118] | |
Middle Molecules, Proteins | |
Immunoglobulin light chains (IgLCs) | PMNLs: chemotaxis ↓, glucose uptake stimulation ↓, glucose uptake basal ↑ [119]; apoptosis ↓ [47] |
Retinol binding protein (RBP) | PMNLs: chemotaxis ↓, oxidative burst ↓, apoptosis ↓ [120] |
Leptin | PMNLs: chemotaxis ↓, oxidative burst ↓ [121] |
Resistin | PMNLs: chemotaxis ↓, oxidative burst ↓ [122] |
Tamm-Horsfall protein (THP) | PMNLs: (high concentrations) apoptosis ↓, chemotaxis ↓, phagocytosis ↑; (low concentrations) chemotaxis ↑ [123] |
High-density lipoprotein (HDL) | Loss of anti-inflammatory properties in uremia [124,125] |
Protein Modifications | |
Glucose-modified proteins | PMNLs: chemotaxis ↑, glucose uptake ↑, apoptosis ↑ [48] |
AGE-modified albumin | Leukocytes: activating, pro- atherogenic [126] |
AGEs | Macrophages: TNF and IL-1 secretion ↑ [127] |
Monocytes: Chemotaxis ↑ [128] | |
Glycated collagen | PMNLs: Adhesion ↑ [129] |
Advanced oxidation protein products (AOPPs) | PMNLs and monocytes: oxidative burst ↑ [130] |
Oxidized low-density lipoproteins (oxLDLs) | Macrophage activation [131]; |
PMNLs and eosinophils: chemotaxis ↑, degranulation ↑ [132]; | |
Regulatory T cells: proteasome activity ↓ → cell cycle arrest and apoptosis [133] | |
Homocysteinylated albumin | Monocytes: adhesion ↑[134] |
6.1. LMW Solutes
6.2. Middle Molecules, Proteins
6.3. Protein Modifications
6.3.1. Advanced Glycation End-Products
6.3.2. Oxidative Modifications
6.3.3. Carbamoylation, Carbonylation and Homocysteinylation
7. Further Aspects of Immune Dysfunction in Uremia
7.1. Antigen-Presenting Cells
7.2. Epigenetics
7.3. Antineutrophil Cytoplasmic Autoantibodies
8. Conclusions
Acknowledgments
Conflict of Interest
References
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Cohen, G.; Hörl, W.H. Immune Dysfunction in Uremia—An Update. Toxins 2012, 4, 962-990. https://doi.org/10.3390/toxins4110962
Cohen G, Hörl WH. Immune Dysfunction in Uremia—An Update. Toxins. 2012; 4(11):962-990. https://doi.org/10.3390/toxins4110962
Chicago/Turabian StyleCohen, Gerald, and Walter H. Hörl. 2012. "Immune Dysfunction in Uremia—An Update" Toxins 4, no. 11: 962-990. https://doi.org/10.3390/toxins4110962