Vitamin D levels reverberate in monocytes modulation in hemodialysis patients.

BACKGROUND: Patients with chronic kidney disease (CKD) have a severe vitamin D deficiency and increasing epidemiological data suggesting that this deficiency may play a role in overall morbidity and mortality associated with CKD. It is known that vitamin D regulates the immune system, however, in dialysis patients this deficiency and the modulation of proinflammatory cells is unclear. Among these, monocytes arouse interest considering they constitutively express vitamin D receptors. AIM: This study aimed the evaluation of monocytic profile in CKD patients according to vitamin D levels. METHODS: Patients in hemodialysis (HD) were divided into two groups, regarding vitamin D levels: Group 1, vitamin D <26 ng/ml (n = 15) and Group 2, vitamin D ≥26 ng/ml (n = 18). Whole blood was collected aiming evaluation of (a) monocytic populations through CD14 and CD16 expression, (b) reactive oxygen species (ROS) generation, and (c) apoptosis. RESULTS: We observed that in Group 1, when compared to Group 2, there was a significant increase in intermediate monocytes (CD14++ CD16 + ; 34.7 ± 31.6 vs. 12.1 ± 6.3; p = 0.006, respectively) and decrease in classical ones (CD14 ++ CD16 - ; 45.3 ± 31.8 vs. 70.4 ± 25.1; p = 0.017, respectively). There was no difference between groups regarding nonclassical monocytes (CD14 + CD16 ++ ), as well as to apoptosis and to ROS generation. CONCLUSION: This study suggests that HD patients with lower vitamin D levels might have an intensified inflammatory outline as intermediate monocytes with an inflammatory pattern are increased in this population, when compared with patients with higher levels of vitamin D.

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

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 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.

Bjcul, a snake venom lectin, modulates monocyte-derived macrophages to a pro-inflammatory profile in vitro.

Macrophages are cells of high plasticity and can act in different ways to ensure that the appropriate immune response remains controlled. This study shows the effects of the C-type Bothrops jararacussu venom lectin (BJcuL) on the activation of human macrophages derived from the U937 cell line. BJcuL binds on the cell surface, and this event is inhibited by its specific carbohydrate. It induced phagocytosis and production of H2O2, and expression of antigen presentation molecules. It also enhanced the production of TNF-α, GM-CSF and IL-6 by macrophages and indirectly induced T cells to an increased production of TNF-α, IFN-γ and IL-6 in the presence of LPS. Our results suggest that BJcuL can modulate macrophage functional activation towards an M1 state.