Inhibition of calcitriol-induced monocyte CD14 expression by uremic toxins: role of purines.
End-stage renal disease is associated with a defect in immunologic functions. Previous studies have demonstrated that uremic ultrafiltrate (UUF) contains factors that suppress calcitriol synthesis and its biological actions. In the present study, the effect of UUF on basal and calcitriol-induced membrane bound CD14 expression of monocytes activated by phorbol 12-myristate 13-acetate was evaluated. CD14 acts as a receptor for the complexes of lipopolysaccharide and lipopolysaccharide-binding protein. Monocytes isolated from normal donors were used for the assay of monocyte CD14 expression. A calcitriol induced rise in monocyte CD14 expression (1966+/-423 to 2421+/-436 fluorescence intensity) was found. However, UUF not only suppressed basal CD14 expression of monocytes (from 1966+/-423 to 1240+/-203, P < 0.05) but also significantly blunted calcitriol-induced CD14 expression (from 2421+/-436 to 1744+/-229, P < 0.05). HPLC fractionated UUF collected from 8 to 16 min (fraction 1, F1) and from 25 to 40 min (fraction 3, F3) also significantly suppressed the expression of CD14. Because purine derivatives coeluted within F1, their effect on monocyte CD14 expression was also tested. Uric acid, xanthine, and hypoxanthine was found to suppress basal as well as calcitriol-induced CD14 expression of monocytes in a dose-dependent manner. In conclusion, UUF contains factors that impair calcitriol activated function of monocytes.
Glorieux
G
G
Department of Internal Medicine, University Hospital, Gent, Belgium.
Hsu
C H
CH
de Smet
R
R
Dhondt
A
A
van Kaer
J
J
Vogeleere
P
P
Lameire
N
N
Vanholder
R
R
D002117:Calcitriol / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D006801:Humans; D019271:Hypoxanthine / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014118:Toxins, Biological / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014511:Uremia / Q000097:blood*; D014527:Uric Acid / Q000494:pharmacology; D019820:Xanthine / Q000494:pharmacology
D003470:Culture Media; D018950:Lipopolysaccharide Receptors; D011687:Purines; D014118:Toxins, Biological; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D002117:Calcitriol