Up-regulation of intracellular calcium, cyclic adenosine monophosphate and fibronectin synthesis in tubuar epithelial cells by complement.
The terminal complement complex C5b-9 is known to participate in inflammatory processes including glomerular or tubulointerstitial injury. Injury appears to be a direct consequence of C5b-9-mediated cell stimulation. In that context we studied activation of tubular epithelial cells by C5b-9 particularly with regard to fibronectin synthesis and the transmembrane signals involved. C5b-9 in sublytic concentrations caused a rise of intracellular calcium and of cAMP, followed by an increase in abundance of fibronectin-specific mRNA and accumulation of protein. Stabilized cAMP or increasing the cAMP level by forskolin enhanced fibronectin synthesis with similar kinetics. The effect of cAMP could be enhanced by adding a calcium ionophore. Since the fibronectin gene is known to have a cAMP-responsive element, the data suggest that C5b-9 increases fibronectin synthesis via generation of cAMP.
Bürger
A
A
Carl-Ludwig-Institut für Physiologie der Universität Leipzig, Germany.
Wagner
C
C
Hug
F
F
Hänsch
G M
GM
D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D015938:Complement Membrane Attack Complex / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation
D015938:Complement Membrane Attack Complex; D005353:Fibronectins; D000001:Calcimycin; D003994:Bucladesine; D003165:Complement System Proteins; D000242:Cyclic AMP; D002118:Calcium