Peritoneal dialysis solutions inhibit the differentiation and maturation of human monocyte-derived dendritic cells: effect of lactate and glucose-degradation products.
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 alpha, interleukin (IL)-6 and IL-12 p70, and nuclear factor (NF)-kappaB 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-kappaB activation. Evaluation of PD components revealed that sodium lactate and glucose-degradation products impaired the acquisition of maturation parameters and NF-kappaB 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.
Puig-Kröger
Amaya
A
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Pello
Oscar Muñiz
OM
Muñiz-Pello
Oscar
O
Selgas
Rafael
R
Criado
Gabriel
G
Bajo
M-Auxiliadora
MA
Sánchez-Tomero
Jose A
JA
Alvarez
Vicente
V
del Peso
Gloria
G
Sánchez-Mateos
Paloma
P
Holmes
Clifford
C
Faict
Dirk
D
López-Cabrera
Manuel
M
Madrenas
Joaquín
J
Corbí
Angel L
AL
D018949:Antigens, CD1 / Q000378:metabolism; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D015314:Dialysis Solutions / Q000633:toxicity*; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism; D010530:Peritoneal Dialysis; D011956:Receptors, Cell Surface / Q000378:metabolism; D019354:Sodium Lactate / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D018949:Antigens, CD1; D015815:Cell Adhesion Molecules; D004247:DNA; D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced; D018664:Interleukin-12; D015850:Interleukin-6; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D019354:Sodium Lactate; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C419393:CD1a antigen