Complement and the direct mediation of immune glomerular injury: A new perspective

Couser, William G.; Baker, Paul E.; Adler, Stephen

doi:10.1038/ki.1985.214

Cited by 142 publications

(65 citation statements)

References 92 publications

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“…Depletion of complement at the end of the disease protocol with cobra venom factor or selective inhibition of C5 reduces proteinuria in this model of GN (33,34). The latter finding, combined with the observation by electron microscopic immunohistochemistry that podocyte membranes stain intensely for C5b-9 (35), implicate C5b-9 -mediated podocyte injury as a cause of proteinuria in this model (36).…”

Section: Discussionmentioning

confidence: 75%

Distinct and Separable Roles of the Complement System in Factor H-Deficient Bone Marrow Chimeric Mice with Immune Complex Disease

Alexander

Aneziokoro

Chang

et al. 2006

Journal of the American Society of Nephrology

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Section: Discussionmentioning

confidence: 75%

Distinct and Separable Roles of the Complement System in Factor H-Deficient Bone Marrow Chimeric Mice with Immune Complex Disease

Alexander

Aneziokoro

Chang

et al. 2006

Journal of the American Society of Nephrology

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“…The fourth component, C4, is critical in the classical pathway only. Activation leads to the production of immunomodulatory split products [16,17] and the assembly of the membrane attack complex (C5b-9), which inserts through cell membranes disrupting intracellular homeostasis and finally leading to cell lysis and death [18]. Mammalian cells express on their surface inhibitors of complement activation which make them resistant to complementmediated lysis [15], but the deposition of sublytic amounts of C5b-9 can occur, leading to altered cellular metabolism.…”

Section: Introductionmentioning

confidence: 99%

Protection against anti-glomerular basement membrane (GBM)-mediated nephritis in C3- and C4-deficient mice

Sheerin

Springall

Carroll

et al. 1997

Clinical and Experimental Immunology

111

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SUMMARYMice rendered completely deficient of the complement components C3 or C4 were used to determine the influence of complement activation in the heterologous phase of the anti-GBM disease model. In wildtype animals the disease is characterized by a neutrophil infiltrate, capillary thrombosis, proteinuria and C3 and C4 deposited within the glomerulus. The early infiltration of neutrophils into the glomeruli is greater in wild-type mice (2 . 8 Ϯ 0 . 3) compared with C3-deficient (1 . 4 Ϯ 0 . 2) and C4-deficient (1 . 2 Ϯ 0 . 003) mice. Deficiency also protects against the subsequent development of proteinuria (2 . 99 Ϯ 1 . 11 mg/24 h, 0 . 059 mg/24 h and 0 . 327 Ϯ 0 . 14 mg/24 h in wild-type, C3-deficient and C4-deficient mice, respectively) and decreases glomerular capillary thrombosis in both C3-and C4-deficient mice. The degree of protection is greater in the C3-deficient than the C4-deficient animals, suggesting both classical and alternative pathway involvement. These studies support a critical role for complement in the development of anti-GBM disease. However, the protective effect of complement deficiency can be broken if the dose of nephritogenic antibody is increased.

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“…Vn and clusterin are often found in a similar distribution [8 10]. A pathogenic role for TCC components has been established in the Heymann model of membranous nephropathy [11,12] and may similarly contribute to tissue damage or dysfunction in many diseases associated with complement activation.…”

Section: Introductionmentioning

confidence: 99%

The kinetics and distribution of C9 and SC5b-9 in vivo: effects of complement activation

Greenstein

Peake

Charlesworth

1995

Clinical and Experimental Immunology

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SUMMARYMany diseases associated wilh complement activation are characterized by tissue deposition of components of the terminal complement complex (TCC). The ninth component of complement (C9) plays an important role in the cytolytic effects, and may contribute to the non-lethal cellregulating functions ofthe TCC [1]. In this study we examined the behaviour of radiolabelled human C9 and its soluble complexed form SC5b-9 in vivo in order to determine the effects of complement activation on its turnover, distribution and molecular size. In normal rabbits the metabolic parameters of'^^I-C9 {median and range) were: plasma half-life (/[/2)25'9 (20-6 29-5) h, fractional catabolic rate (FCR) 5-7 (5'3-7'0)%/h. and extravascular/lntravascular ratio (EV/IV) 0'7 (0-6-11). The distribution of radiolabelled C9 amongst body tissues was similar to that observed for rabbit serum albumin (RSA). Activation ofthe complement cascade with i.v. injection of cobra venom factor (CVF) resulted in rapid disappearance of C9 from the plasma and accumulation of protein-bound radiolabel in the spleen (exceeding !he plasma concentration) and the liver. RSA metabolism and distribution were unaffected by CVF. Fine performance liquid chromatography (FPLC) gel filtration of plasma samples suggested that monomeric C9 was the only major radiolabelled protein present during normal turnovers, whereas CVF administration was accompanied by the prompt appearance of a high mol. wt species consistent in size with SC5b-9. When injected directly, '"^I-SC5b-9 disappeared rapidly from the plasma, falling by 50% in 0 7 (0-6-()-8) h, and less than 15% remaining after 4 h with accumulation of protein-bound label in the spleen and liver. These results demonstrate the complexity of C9 metabolism during complement activation.Keywords C9 terminal complement complex metabolic turnover tissue distribution SC5b-9

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Complement and the direct mediation of immune glomerular injury: A new perspective

Cited by 142 publications

References 92 publications

Distinct and Separable Roles of the Complement System in Factor H-Deficient Bone Marrow Chimeric Mice with Immune Complex Disease

Distinct and Separable Roles of the Complement System in Factor H-Deficient Bone Marrow Chimeric Mice with Immune Complex Disease

Protection against anti-glomerular basement membrane (GBM)-mediated nephritis in C3- and C4-deficient mice

The kinetics and distribution of C9 and SC5b-9 in vivo: effects of complement activation

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