Induction of Mediator Release from Human Glomerular Mesangial Cells by the Terminal Complement Components C5b-9

Schönermark, Matthias P.; Deppisch, Reinhold; Riedasch, G.; Rother, Klaus; Hänsch, Gertrud Maria

doi:10.1159/000235517

Cited by 58 publications

(30 citation statements)

References 12 publications

(16 reference statements)

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“…In doses ranging from 0.02 to 2 ng/ml/105 GMC, TGFPl did not stimulate a measurable release of TNFa, IL-1 or IL-6 into the cell supernatant, despite the fact that the GMC released these cytokines in response to recornbinant IL-1P. In agreement with the literature, 24 h after addition of IL-Ip, a minor release of TNFa, but a considerable release of IL-1p and IL-6, was seen (data summarized in Table 3) (Schonermark et al, 1991;Zoja et al, 1991).…”

Section: Effect Of Tgfp On Cytokine Releasesupporting

confidence: 88%

Matrix protein synthesis by glomerular mesangial cells in culture: Effects of transforming growth factor β (TGFβ) and platelet‐derived growth factor (PDGF) on fibronectin and collagen type IV mRNA

Hänsch

Wagner

Bürger

et al. 1995

Journal Cellular Physiology

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The pathogenesis of glomerular scarring is multifactional; recent evidence suggests that transforming growth factor beta (TGF beta), a pleiotropic cicatricial mediator, may promote mesangial sclerosis by enhancing the production of extracellular matrix proteins. We studied the effect of TGF beta 1 and TFG beta 2 on collagen type IV and fibronectin (FN) synthesis in human glomerular mesangial cells in culture (GMC). Two hours after addition of TGF beta, an up to twofold increase in abundance of collagen type IV mRNA was found, which further increased up to fivefold within 24 h. Addition of cycloheximide did not inhibit the TGF beta effect, but caused by itself an up to twofold increase in the abundance of collagen type IV mRNA after 2 h. Together with collagen mRNA, the mRNA for FN and for platelet-derived growth factor (PDGF) was also enhanced. PDGF was found to enhance abundance of the collagen type IV and fibronectin mRNA in GMC. A neutralizing antibody to PDGF or a PDGF-antisense oligonucleotide partly inhibited the TGF beta-induced increase of collagen type IV mRNA, suggesting that TGF beta can affect the collagen type IV synthesis not only directly but also indirectly via the synthesis of PDGF.

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Section: Effect Of Tgfp On Cytokine Releasesupporting

confidence: 88%

Matrix protein synthesis by glomerular mesangial cells in culture: Effects of transforming growth factor β (TGFβ) and platelet‐derived growth factor (PDGF) on fibronectin and collagen type IV mRNA

Hänsch

Wagner

Bürger

et al. 1995

Journal Cellular Physiology

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“…First, MAC has been shown to cause proliferation of glomerular mesangial, endothelial, and epithelial cells in vitro and therefore may be directly involved in inducing a increase in intrinsic cell number (17,21,44,45). Additionally, there are data indicating that MAC can induce the synthesis and/or secretion of a number of proinflammatory cytokines such as TNF-␣ and IL-1 (22,44), adhesion molecules such as ICAM-1 and E selectin (23), and chemokines such as IL-8 (46) and that these effects may play a role in the infiltration of cells to the glomerulus. We have also demonstrated that later in the progression of ANTN, mCd59a deficiency, by allowing unregulated MAC deposition, exacerbates glomerular thrombosis.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that sublethal MAC can mediate proliferative, proinflammatory and profibrotic effects in vitro in glomerular cells (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). MAC has also been shown to be involved in the pathogenesis of a number of glomerular diseases in vivo, including membranous nephropa-thy (24,25) and immune complex nephritis (26,27).…”

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confidence: 99%

CD59a Deficiency Exacerbates Accelerated Nephrotoxic Nephritis in Mice

Turnberg¹,

Botto²,

Warren³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. CD59 is a complement regulatory protein that inhibits the terminal part of the complement system, the membrane attack complex (MAC), a mediator of renal injury. Mice deficient in the Cd59a gene (mCd59aϪ/Ϫ) were used to investigate the role of CD59 in experimentally induced accelerated nephrotoxic nephritis, a model of immune complex-mediated glomerulonephritis. After accelerated nephrotoxic nephritis was induced by administration of sheep nephrotoxic globulin, mCd59aϪ/Ϫ mice and strain-matched controls on two genetic backgrounds, 129/Sv ϫ C57BL/6 and 129/Sv, were examined. For both, mCd59aϪ/Ϫ mice developed significantly greater glomerular cellularity than wild-type (WT) mice at day 5 after administration. At day 10 post-administration, mCd59aϪ/Ϫ mice exhibited more glomerular thrombosis than WT mice (thrombosis score, 1.8 [range, 1.4 to 4.0] versus 0.8 [range, 0.2 to 1.5] quadrants thrombosed per glomerulus, respectively; P ϭ 0.0006). In the majority of experiments, mCd59aϪ/Ϫ mice also had significantly more proteinuria than controls; however, there was no difference in serum creatinine or albumin. Quantitative immunofluorescence of kidney sections revealed significantly more C9 (as a marker of MAC) deposition within glomeruli of mCd59aϪ/Ϫ mice than WT controls (P Ͻ 0.001). There was no difference in deposition of C3 and sheep IgG between the two experimental groups. The lack of CD59a, by allowing unregulated MAC deposition, exacerbates the renal injury in this model of immune complex-mediated glomerulonephritis.

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“…In experimental glomerulonephritis, the membrane attack complex (MAC) frequently plays an important role in causing cell-lysis. [23][24][25][26] In this low-dose model, the influence of MAC is probably milder than in the high-dose model. Neutrophils also play an important role in the induction and progression of nephritis.…”

Section: Discussionmentioning

confidence: 99%

Experimental glomerulonephritis induced by a low dose of anti-thy-1 antibody

et al. 1997

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Background: Thy-1.1 nephritis is a widely used model of proliferative glomerulonephritis. Lesions are characterized by diffuse mesangiolysis and prominent ballooning of capillary loops, followed by severe mesangial proliferation. However, such severe lesions are not common in human mesangial proliferative nephritis. We analyzed mild-to-moderate mesangial proliferative nephritis induced by a lower dose of anti-Thy-1.1 antibody. Methods" We administered a low intravenous dose (0.02 mg/mL) of antibody to Wistar rats, and the histologic changes were observed by light and electron microscopy and by various immunopathologic methods. The serum complement level and distribution of polymorphonuclear leukocytes were also examined. Results" Diffuse mesangial-cell lysis occurred at day 1, but mesangial-matrix lysis was mild, and ballooning of capillary loops was rare. Mesangia] cell proliferation appeared at day 2 and reached its maximum at day 5, but it was milder than that seen in the usual dose (0.2 mg/mL) model. The glomerulus was repaired to almost normal structure by day 14. Residual mesangial matrices and endothelial cells seemed to prevent ballooning by making bridges with capillary basement membranes. In the healing stage, this low-dose model demonstrated mild vascular remodeling without active angiogenesis, while the usual-dose model of Thy-1 nephritis showed prominent angiogenic activity to reconstruct capillary tufts. Conclusion:The low-dose model of Thy-1 nephritis, which does not require prominent angiogenesis, may be more useful in analyzing the mechanism of glomerulonephritis than the usually adopted Thy-1 nephritis model, which showed drastic glomerular destruction and prominent angiogenesis.

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Induction of Mediator Release from Human Glomerular Mesangial Cells by the Terminal Complement Components C5b-9

Cited by 58 publications

References 12 publications

Matrix protein synthesis by glomerular mesangial cells in culture: Effects of transforming growth factor β (TGFβ) and platelet‐derived growth factor (PDGF) on fibronectin and collagen type IV mRNA

Matrix protein synthesis by glomerular mesangial cells in culture: Effects of transforming growth factor β (TGFβ) and platelet‐derived growth factor (PDGF) on fibronectin and collagen type IV mRNA

CD59a Deficiency Exacerbates Accelerated Nephrotoxic Nephritis in Mice

Experimental glomerulonephritis induced by a low dose of anti-thy-1 antibody

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