p-Cresyl sulfate affects the oxidative burst, phagocytosis process, and antigen presentation of monocyte-derived macrophages

- Lowest pCS concentrations induce ROS production and increases phagocytosis.
- Highest pCS concentrations diminish its ability to activate the immune cells.
- No modulation of HLA-DR or CD86 expression was induced by pCS.

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 × 106 cells/mL) were incubated with pCS (10, 25, or 50 μg/mL), with or without lipopolysaccharide (LPS; 25 ng/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 6 h incubation but only the lowest concentration increased this production after 12 h (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 (50 μg/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.