Peritoneal dialysis solutions inhibit the differentiation and maturation of human monocyte-derived dendritic cells: effect of lactate and glucose-degradation products

• Published in: Journal of leukocyte biology Vol. 73; no. 4; pp. 482 - 492
• Main Authors: Puig-Kröger, Amaya, Muñiz-Pello, Oscar, Selgas, Rafael, Criado, Gabriel, Bajo, M-Auxiliadora, Sánchez-Tomero, Jose A, Alvarez, Vicente, del Peso, Gloria, Sánchez-Mateos, Paloma, Holmes, Clifford, Faict, Dirk, López-Cabrera, Manuel, Madrenas, Joaquín, Corbí, Angel L
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.04.2003
• Subjects: Antigens, CD1 - metabolism; Blotting, Western; Cell Adhesion Molecules - metabolism; Cell Differentiation - drug effects; Cell Division - drug effects; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Dialysis Solutions - toxicity; DNA - metabolism; Electrophoretic Mobility Shift Assay; Flow Cytometry; Glycation End Products, Advanced - toxicity; Humans; IL‐12; IL‐6; immune response; Interleukin-12 - metabolism; Interleukin-6 - metabolism; Lectins, C-Type - metabolism; Lipopolysaccharides - pharmacology; Monocytes - cytology; NF-kappa B - metabolism; NF‐κB; Peritoneal Dialysis; Receptors, Cell Surface - metabolism; Sodium Lactate - toxicity; TNF‐α; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0902451

Peritoneal dialysis (PD) is a well‐established therapy for end‐stage renal failure, but its efficiency is limited by recurrent peritonitis. As PD solutions impair local inflammatory responses within the peritoneal cavity, we have analyzed their influence on the in vitro maturation of human monocyte‐derived dendritic cells (MDDC). Evaluation of MDDC maturation parameters [expression of adhesion and costimulatory molecules, receptor‐mediated endocytosis, allogeneic T cell activation, production of tumor necrosis factor α, interleukin (IL)‐6 and IL‐12 p70, and nuclear factor (NF)‐κB activation] revealed that currently used PD solutions differentially inhibit the lipopolysaccharide (LPS)‐induced maturation of MDDC, an inhibition that correlated with their ability to impair the LPS‐stimulated NF‐κB activation. Evaluation of PD components revealed that sodium lactate and glucose‐degradation products impaired the acquisition of maturation parameters and NF‐κB activation in a dose‐dependent manner. Moreover, PD solutions impaired monocyte‐MDDC differentiation, inhibiting the acquisition of DC markers such as CD1a and DC‐specific intercellular adhesion molecule‐3 grabbing nonintegrin (CD209). These findings have important implications for the initiation of immune responses under high lactate conditions, such as those occurring within tumor tissues or after macrophage activation.