Local secretion of complement C3 in the exocrine pancreas: Ductal epithelial cells as a possible biosynthetic site

Background & Aims: The complement system participates in the local immune system in various tissues, In this study, we investigated the local secretion of complement C3 into the pancreatic fluid and attempted to determine a possible biosynthetic site, Methods: C3 protein in human pancreatic fluid was analyzed by immunoblotting. The C3 messenger RNA (mRNA) expression in several pancreatic carcinoma cell lines was analyzed by the polymerase chain reaction and/or Northern blotting, The secretion of C3 by these pancreatic carcinoma cells was assessed by metabolic labeling and immunoprecipitation experiments, Results: In five samples of human pancreatic fluid, C3 was detected as a molecule composed of alpha and beta chains, C3 mRNA expression was observed in the ductal cell carcinoma lines (PANC-1 and MIA PaCa-2) but not in the acinar cell line (HPC-YO and AR-42J), C3 production in these cells was enhanced by interleukin 1 beta and tumor necrosis factor alpha at both the protein and the mRNA levels. Conclusions: (1) Complement C3 is secreted into the exocrine fluids of the pancreas, (2) Ductal epithelial cells are possible biosynthetic sites for C3, (3) The proinflammatory cytokines, interleukin 1 beta and tumor necrosis factor alpha are effective stimulators of local C3 production in the pancreas.