Interleukin 2 mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells.
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.
Brooimans
R A
RA
Department of Nephrology, University Hospital, Leiden, The Netherlands.
Stegmann
A P
AP
van Dorp
W T
WT
van der Ark
A A
AA
van der Woude
F J
FJ
van Es
L A
LA
Daha
M R
MR
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
D003176:Complement C3; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2