Differential expression of complement C3 and C4 in the human kidney.

Welch, Thomas R.; Beischel, Linda; Witte, David P.

doi:10.1172/jci116722

Cited by 95 publications

(67 citation statements)

References 18 publications

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“…All in all, the balance between the degree of production of IL-1 , TNF-and IFN-at the local site may determine the final outcome of the inflammation by fine regulation of the production of IL-8 or other chemotactic cytokines or complement components at the local site [16][17][18][19]35]. In case of upregulation of IL-8, the influx of neutrophils may lead to an increase of the local inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro it has been shown that mesangial cells and renal cell carcinomas can produce IL-8 in response to inflammatory cytokines [12][13][14][15]. Since it is known that human proximal tubular epithelial cells produce cytokines and complement components in response to inflammatory cytokines both in vitro and in vivo [16][17][18][19], we postulated that human proximal tubular epithelial cells (PTEC) potentially could be a source of IL-8. In addition, we investigated the effect of proinflammatory cytokines on the production of IL-8 by PTEC.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro

Gerritsma¹,

Hiemstra

Gerritsen³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYA number of inflammatory kidney diseases are associated with interstitial nephritis and influx of leucocytes in the renal interstitium. Potentially the influx of neutrophils in the interstitium may be induced by the chemotactic cytokine IL-8. In the present study we have analysed the production of IL-8 by cultured human proximal tubular epithelial cells (PTEC) in response to a number of proinflammatory cytokines. Primary cell lines of proximal tubular epithelium obtained from ten different kidneys, and cultured under serum-free conditions, were found to produce IL-8 to different degrees from not detectable levels up to 10

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro

Gerritsma¹,

Hiemstra

Gerritsen³

et al. 1996

Clinical and Experimental Immunology

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“…Expression of C3 in the kidney and its deposition there in IC glomerulonephritis in humans suggests a pathogenic role for C3 in renal immunopathology (8). C3 expression and deposition has also been documented in IC-mediated glomerulonephritis, in both induced rodent models (e.g., Ag-or autoantibody-injected mice) as well as spontaneous lupus models (e.g., MRL/lpr and NZB/NZW F 1 mice) (9 -11).…”

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confidence: 99%

Complement Component C3 Is Not Required for Full Expression of Immune Complex Glomerulonephritis in MRL/lprMice

Sekine

Reilly

Molano

et al. 2001

The Journal of Immunology

134

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Complement activation and tissue deposition of complement fragments occur during disease progression in lupus nephritis. Genetic deficiency of some complement components (e.g., Factor B) and infusion of complement inhibitors (e.g., Crry, anti-C5 Ab) protect against inflammatory renal disease. Paradoxically, genetic deficiencies of early components of the classical complement pathway (e.g., C1q, C4, and C2) are associated with an increased incidence of lupus in humans and lupus-like disease in murine knockout strains. Complement protein C3 is the converging point for activation of all three complement pathways and thus plays a critical role in biologic processes mediated by complement activation. To define the role of C3 in lupus nephritis, mice rendered C3 deficient by targeted deletion were backcrossed for eight generations to MRL/lpr mice, a mouse strain that spontaneously develops lupus-like disease. We derived homozygous knockout (C3−/−), heterozygous (C3+/−), and C3 wild-type (C3+/+) MRL/lpr mice. Serum levels of autoantibodies and circulating immune complexes were similar among the three groups. However, there was earlier and significantly greater albuminuria in the C3−/− mice compared with the other two groups. Glomerular IgG deposition was also significantly greater in the C3−/− mice than in the other two groups, although overall pathologic renal scores were similar. These results indicate that C3 and/or activation of C3 is not required for full expression of immune complex renal disease in MRL/lpr mice and may in fact play a beneficial role via clearance of immune complexes.

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“…In these examples, strong intraglomerular expression of complement occurs. 4,7,17 Mesangiocapillary glomerulonephritis is reproduced spontaneously in mice lacking the soluble complement regulator, factor H, 18 demonstrating that loss of complement regulation alone can be a powerful cause of glomerular inflammation. However, despite expectations for local production of complement to play an instrumental role, only the circulating components contribute to glomerular inflammation in these mice.…”

Section: Glomerular Diseasementioning

confidence: 99%

“…3 Glomerular disease shows expansion of complement genes in glomerular mesangial and epithelial cells, whereas primary tubulointerstitial disease is linked with synthesis predominantly in the tubular epithelium. 4 However, induction of glomerular disease in experimental models is soon followed by expression of complement genes in the proximal tubule, a pattern that also typifies chronic human glomerulonephritis. 4,5 This wave of expression of complement genes radiating from glomeruli to proximal tubules foretells a significant shift in the role of local complement in progressive renal disease (Table 1).…”

mentioning

confidence: 99%