title: p-Cresyl sulfate affects the oxidative burst, phagocytosis process, and antigen presentation of monocyte-derived macrophages.
abstract: Immune system dysfunction is a common condition in chronic kidney disease (CKD). The present study investigated the effect of p-Cresyl sulfate (pCS) on human cell line U937 monocyte-derived macrophages (MDM) activity. MDM (1×106cells/mL) were incubated with pCS (10, 25, or 50μg/mL), with or without lipopolysaccharide (LPS; 25ng/mL) and then evaluated NO production, phagocytosis and antigen-presenting molecules expression (HLA-ABC, HLA-DR, CD80 and CD86). All analyses were performed by flow cytometry. All pCS concentrations were able to increase NO production (49±12.1%, 39.8±7.75%, 43.7±11.9%, respectively) compared to untreated cells (4.35±3.34%) after 6h incubation but only the lowest concentration increased this production after 12h (82.9±8.6%, 61±7.2%, 40.8±11.7%). Combined with LPS, the same results were observed. Regarding to phagocytosis, all concentrations were able to induce bead engulfment (35.4±2.71%, 30±3.04%, 23.28±4.58%). In addition, pCS (50μg/mL) was able to increase HLA-ABC and CD80 expression, showed a slight effect on HLA-DR expression and, no difference in basal CD86 levels. pCS can induce an increased oxidative burst and phagocytosis by human macrophages while no modulation of HLA-DR or CD86 expression was induced. Together, these results suggest that pCS induces macrophage activation but interfere in antigen processing, leading to a failure in adaptive immune response in CKD.
authors.affiliation: Pontifícia Universidade Católica do Paraná, PUCPR, Brazil.
authors.forename: M L V
authors.initials: ML
authors.lastname: Azevedo
authors.affiliation: Pontifícia Universidade Católica do Paraná, PUCPR, Brazil.
authors.forename: N B
authors.initials: NB
authors.lastname: Bonan
authors.affiliation: Pontifícia Universidade Católica do Paraná, PUCPR, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Dias
authors.affiliation: Pontifícia Universidade Católica do Paraná, PUCPR, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Brehm
authors.affiliation: Pontifícia Universidade Católica do Paraná, PUCPR, Brazil.
authors.forename: T M
authors.initials: TM
authors.lastname: Steiner
authors.affiliation: Laboratory of Bacteriology, Department of Clinical Analysis, UFPR, Brazil.
authors.forename: W M
authors.initials: WM
authors.lastname: Souza
authors.affiliation: Basic Pathology Department, Laboratory of Experimental Nephrology, UFPR, Brazil.
authors.forename: A E M
authors.initials: AE
authors.lastname: Stinghen
authors.affiliation: Pontifícia Universidade Católica do Paraná, PUCPR, Brazil.
authors.forename: F C
authors.initials: FC
authors.lastname: Barreto
authors.affiliation: Pontifícia Universidade Católica do Paraná, PUCPR, Brazil.
authors.forename: Selene
authors.initials: S
authors.lastname: Elifio-Esposito
authors.affiliation: Pontifícia Universidade Católica do Paraná, PUCPR, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Pecoits-Filho
authors.affiliation: Pontifícia Universidade Católica do Paraná, PUCPR, Brazil. Electronic address: andrea.moreno@pucpr.br.
authors.forename: A N
authors.initials: AN
authors.lastname: Moreno-Amaral
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects*; D000975:Antioxidants / Q000378:metabolism; D018122:B7-1 Antigen / Q000096:biosynthesis; D003408:Cresols / Q000633:toxicity*; D006680:HLA Antigens / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects*; D013463:Sulfuric Acid Esters / Q000633:toxicity*; D020298:U937 Cells; D014511:Uremia / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018122:B7-1 Antigen; D003408:Cresols; D006680:HLA Antigens; D008070:Lipopolysaccharides; D013463:Sulfuric Acid Esters; D009569:Nitric Oxide; C408690:4-cresol sulfate
keywords: Innate immune response; Monocyte-derived macrophage; Uremia; Uremic toxins; p-Cresyl sulfate