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.