Regulation of complement C3 and C4 synthesis in human peritoneal mesothelial cells by peritoneal dialysis fluid.
Although complement is activated in the peritoneal cavity during chronic peritoneal dialysis (PD), little is known about its role in peritoneal defence and injury related to long-term PD. We examined the impact of glucose and commercial peritoneal dialysis solutions on complement expression in HPMCs obtained by primary culture from omental tissues of consented patients undergoing elective abdominal surgery. Constitutive expression of C3 and C4 mRNA in HPMCs was up-regulated upon exposure to 75 mm glucose in a time-dependent manner. C3 and C4 protein was secreted in both apical and basolateral directions. Glucose doses beyond 100 mm markedly down-regulated C3 and C4 expression, and stimulated LDH release dose-dependently. Such cytotoxic effects were attenuated using equivalent doses of mannitol instead of glucose. Treatment with conventional lactate-buffered dialysis solution gave rise to down-regulation of C3 and C4 expression, and heightened LDH release in HPMCs. These effects correlated with the glucose strength of the solution, persisted despite replacement with a bicarbonate-buffered solution, aggravated by glycated albumin, and were partially abrogated by supplementation with 10% fetal bovine serum in the culture system. Our findings suggest that the artificial conditions imposed by PD lead to alterations in local complement synthesis that have implications for the role of the peritoneal mesothelium in both inflammation and defence.
Tang
S
S
Department of Nephrology and Transplantation, Guy's, King's College and St Thomas' Hospitals' Medical School, King's College London, UK.
Leung
J C K
JC
Chan
L Y Y
LY
Tsang
A W L
AW
Chen
C X R
CX
Zhou
W
W
Lai
K N
KN
Sacks
S H
SH
D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis* / Q000235:genetics; D003181:Complement C4 / Q000096:biosynthesis* / Q000235:genetics; D015314:Dialysis Solutions / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008353:Mannitol / Q000494:pharmacology; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics
D003176:Complement C3; D003181:Complement C4; D015314:Dialysis Solutions; D012333:RNA, Messenger; D008353:Mannitol; D005947:Glucose