C5b-8 and C5b-9 modulate the collagen release of human glomerular epithelial cells.
Aside from their lytic function the late complement components C5b-9 stimulate release of prostanoids, interleukin 1 and oxygen radicals from a number of cells. Since C5b-9 has also been connected to the development of sclerosis in animal models of glomerulonephritis, we addressed the question whether C5b-9 would affect the collagen synthesis. We used human glomerular epithelial cells (GEC) obtained as primary outgrowth cultures. The cells were cultivated in the presence of 14C-proline. Collagen synthesis was quantitated by counting the radioactivity associated with collagenase digestible material. Furthermore, collagen was analyzed by SDS-PAGE. GEC in culture produce spontaneously some collagen type IV. Addition of sublytic doses of highly purified C5b-9 increased the collagen synthesis considerably within 12 to 24 hours. In the absence of C9, C5b-8 stimulated collagen synthesis to a similar extent, whereas in the absence of C7 or C8, the collagen synthesis was not enhanced. Furthermore, fluid-phase-formed C5b-9 complexes did not stimulate the collagen synthesis, indicating that assembly of the complex on the target membrane was required. Since C5b-9 deposits are found in sclerotic areas, our data support the hypothesis that C5b-9, by stimulating collagen synthesis as well as release, might contribute to the development of chronic nephritis.
Torbohm
I
I
Institut für Immunologie, Universität Heidelberg, Federal Republic of Germany.
Schönermark
M
M
Wingen
A M
AM
Berger
B
B
Rother
K
K
Hänsch
G M
GM
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000378:metabolism / Q000494:pharmacology*; D003165:Complement System Proteins / Q000378:metabolism / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D015938:Complement Membrane Attack Complex; C042295:complement C5b-8 complex; D003094:Collagen; D003165:Complement System Proteins