title: Interleukin 2 mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells.
abstract: Previous reports have suggested the production of complement components C4, C2, and factor B by renal tissue. However, the cells involved in production of complement have not been identified. In this study metabolic labeling experiments demonstrated that human proximal tubular epithelial cells (PTEC) synthesize a 180-kD precursor of C3 that is secreted after proteolytic cleavage into a disulphide linked two-chain molecule as found in plasma. C3 present in culture supernatants of PTEC was functionally active, however, during the culture period there was a partial inactivation of the C3 molecule as assessed by hemolytic titration. Recombinant IL-2 enhances the rate of C3 synthesis in a dose-dependent manner reaching maximal stimulation at doses of 200-400 U/ml IL-2. Northern blot analysis demonstrated a 5.2-kb C3 mRNA species present in PTEC that was increased within 24 h of IL-2 treatment. IL-2-induced enhancement of C3 production by PTEC could be neutralized with specific antibodies to IL-2. This study demonstrates that C3 synthesis in PTEC is upregulated by IL-2, the major cytokine produced by activated T cells.
authors.affiliation: Department of Nephrology, University Hospital, Leiden, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Brooimans
authors.forename: A P
authors.initials: AP
authors.lastname: Stegmann
authors.forename: W T
authors.initials: WT
authors.lastname: van Dorp
authors.forename: A A
authors.initials: AA
authors.lastname: van der Ark
authors.forename: F J
authors.initials: FJ
authors.lastname: van der Woude
authors.forename: L A
authors.initials: LA
authors.lastname: van Es
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis* / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D015375:Receptors, Interleukin-2 / Q000032:analysis
chemical_list: D003176:Complement C3; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2