HSP induction in mesothelial cells by peritoneal dialysis fluid depends on biocompatibility test system

Background: We have previously shown that exposure of mesothelial cells (MC) to peritoneal dialysis fluids (PDF) not only caused toxic injury, but also induced cytoprotective heat shock proteins (HSP). This study was performed in order to compare HSP expression in MC upon PDF exposure in three currently used biocompatibility test systems. Methods: Omentum-derived human peritoneal MC underwent 3 modalities of exposure to heat-or filter-sterilized PDF: (A) pure PDF for 60 minutes followed by a recovery-period in pure culture medium for 24 hours; (B) 1: 1 mixture of PDF and culture medium for 24 hours or (C) pure PDF for 60 minutes followed by a recovery-period in a 1: 1 mixture of PDF and culture medium for 24 hours. Biocompatibility was assessed by LDH-release into the supernatant and HSP-72 expression in MC lysates. Results: Short-term exposure of MC to pure PDF (Modality A) resulted in concordant LDH release and upregulation of HSP-72, regardless of heat or filter sterilization. In contrast, both test systems that exposed MC to heat-sterilized PDF during the recovery period (Modalities B and C) resulted in severe cellular lethality but low HSP-72 expression. Conclusions: This study clearly shows that HSP expression in MC upon PDF exposure depends on the biocompatibility test system. The presence of heat-sterilized PDF during recovery resulted in significant downregulation of Hsp-72 despite severe cell injury. Therefore, Hsp-72 expression reflects adequate cellular stress responses rather than PDF cytotoxicity.