The uraemic toxin phenylacetic acid contributes to inflammation by priming polymorphonuclear leucocytes

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Abstract

Background The activation of polymorphonuclear leucocytes (PMNLs) causes inflammation and as a result cardiovascular disease, which is a main risk factor for increased morbidity and mortality in patients with chronic kidney disease. Toxins accumulating in uraemic patients play a major role in modulating essential PMNL functions and apoptosis, the latter being crucial for a coordinated resolution of inflammation. One uraemic toxin is phenylacetic acid (PAA). We therefore investigated whether PAA contributes to the deranged immune response in uraemia by modulating PMNL activities.MethodsPMNL oxidative burst, phagocytosis and surface expression of the activation markers CD11b and CD18 were measured by flow cytometry in whole blood from healthy subjects in the presence and absence of PAA. Spontaneous apoptosis of isolated PMNLs was assessed by evaluating morphological features under the fluorescence microscope and by measuring the DNA content by flow cytometry. PMNL chemotaxis was tested by the under-agarose method.ResultsPAA significantly enhanced the stimulation of PMNL oxidative burst by Escherichia coli, phagocytosis of E. coli by PMNLs and the expression of CD11b and CD18 at the PMNL surface. PAA significantly decreased PMNL apoptosis resulting in an increased percentage of viable cells. PAA affected neither the oxidative burst stimulated by phorbol-12-myristate-13- acetate nor PMNL chemotaxis.ConclusionsPAA increases the activation of various PMNL functions and the expression of surface activation markers, while it attenuates PMNL apoptotic cell death. Therefore, PAA may contribute to the inflammatory state and consequently to increased cardiovascular risk in uraemic patients. © 2012 The Author.

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Cohen, G., Raupachova, J., & Hörl, W. H. (2013). The uraemic toxin phenylacetic acid contributes to inflammation by priming polymorphonuclear leucocytes. Nephrology Dialysis Transplantation, 28(2), 421–429. https://doi.org/10.1093/ndt/gfs454

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