Excessive salt intake may result in the development of hypertension. Recent studies indicated that high sodium concentrations polarize the T-cell immune response toward TH17. Moreover, high salt diet increases interstitial sodium concentration (up to 180 mol/L) and skin macrophage and dendritic cell (DC) density. Furthermore, hypertension was shown to be transferable from hypertensive to normotensive animals through infusion of DC from hypertensive animals. However, the effects of high sodium concentration on DC function remain unknown.Design and method:
In this study we analyzed how high Sodium Chloride (NaCl) concentration interferes with in vitro human DC differentiation and maturation. DC were derived from human blood monocytes that were differentiated for 6 days into DCs in RPMI 10% Bovine calf serum supplemented with GM-CSF (66 ng/ml) and IL4 (25 ng/ml) then stimulated during 48 h with LPS 2.5 ng/ml at different concentrations of NaCl [140 -160 -180 -200 mmol/L]. We analyzed cell viability by Annexin V and Propidium iodide staining and cell expression of CCR7, CD25, CD80, CD86 and CD83 by flow cytometry. We also studied monocyte differentiation into DC with different NaCl concentrations by DC-sign staining.Results:
DC viability was excellent up to 180 mmol/L [NaCl] (>90%), and started to decrease to reach 57% for 200 mmol/L [NaCl]. DC-sign expression during monocyte differentiation into DC decreased with increasing NaCl concentration (86.7% vs 37.2% for 140 vs 200 mmol/L, respectively). High NaCl concentration reduced the expression of maturation markers (CD25 + CD80 + : 91.3 ± 2.8 vs 79.6 ± 5.9%; CD25 + CD86 + : 92.5 ± 4.4 vs 77.2 ± 3.0%; CD25 + CD83 + : 91.8 ± 4.4 vs 77.2 ± 5.6%) for 140 mmol/L and 200 mmol/L NaCl, respectively. Of note, the expression of CCR7 diminished from (47.4 ± 12.5 to 19.4 + 12.2%) for 140 mmol/L and 200 mmol/L.Conclusions:
High NaCl concentration delays the differentiation of human monocytes into DC, and inhibits the DC maturation and migration process thus educing immunostimulatory capacity. Whether DC submitted to high NaCl concentrations may polarize the T-cell response remains unknown.