Early- and Late-Phase Activation of
Complement Evaluated by Plasma Levels of C3d,g and
the Terminal Complement Complex

Mollnes, Tom Eirik

doi:10.1159/000467856

Cited by 57 publications

(30 citation statements)

References 19 publications

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“…the spleen and liver were sites of sequestration of protein-bound '^^1 in rabbits injected with '^"'*I-SC5b-9 directly, while levels in the kidneys, lungs, heart and skeletal muscle were similar to plasma. '"^i-SC5b-9 was ehminated rapidly from the plasma (time to 50% 0-6-0-8h) with < 15% of the injected dose remaining after 4 h. This resuit is consisteni with previous measurements of SC5b-9 clearance in man and rabbits [21][22][23]. We were unable, however, to calculate the true piasma /1/2, FCR and EV/IV distribution for SC5b-9 due to its rapid clearance and iack of equilibration across body compartments.…”

Section: Discussionsupporting

confidence: 82%

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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Section: Discussionsupporting

confidence: 82%

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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“…Another reason may be the differences in clearance between C5a and TCC. In principle, C5a and TCC are formed in equimolar quantities, but fluid-phase TCC (SC5b-9) has a longer half-life (50 minutes) [19] than C5a (1 to 2 minutes) [1, 2]. The positive correlation between whole-blood C5a (ie, cell-associated and plasma C5a) and TCC also shows that TCC is an indirect indicator of total C5a generation.…”

Section: Commentmentioning

confidence: 99%

Both Plasma- and Leukocyte-Associated C5a Are Essential for Assessment of C5a Generation In Vivo

Hetland¹,

Moen²,

Bergh³

et al. 1997

The Annals of Thoracic Surgery

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“…They confirm that TCC has a short t112 in vivo. This tl12 has been estimated to 30-50 min in rabbits (33) and 50 min in humans (34). A relatively high concentration of FH was necessary to suppress C activation in vivo since 30 ml/ kg corresponds to about half the normal plasma volume in piglets.…”

mentioning

confidence: 99%

Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.

Høgåsen

Jansen²,

Mollnes³

et al. 1995

J. Clin. Invest.

200

141

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We have recently described hereditary membranoproliferative glomerulonephritis type II in the pig. All affected animals had excessive complement activation, revealed as low plasma C3, elevated plasma terminal complement complex, and massive deposits of complement in the renal glomeruli, and eventually died of renal failure within 11 wk of birth. The aim of the present study was to investigate the cause of complement activation in this disease. Transfusion of normal porcine plasma to affected piglets inhibited complement activation and increased survival. Plasma was successively fractionated and the complement inhibitory effect of each fraction tested in vivo. A single chain 150-kD protein which showed the same complement inhibitory effect as whole plasma was finally isolated. Immunologic cross-reactivity, functional properties, and NH2-terminal sequence identified the protein as factor H. By Western blotting and enzyme immunoassay, membranoproliferative glomerulonephritisaffected piglets were demonstrated to be subtotally deficient in factor H. At 1 wk of age, median (range) factor H concentration was 1.6 mg/liter (1.1-2.3) in deficient animals (n = 13) and 51 mg/liter (26-98) in healthy littermates (n = 52). Our data show that hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency. (J. Clin. Invest. 1995. 95:1054-1061

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Early- and Late-Phase Activation of Complement Evaluated by Plasma Levels of C3d,g and the Terminal Complement Complex

Cited by 57 publications

References 19 publications

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

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

Both Plasma- and Leukocyte-Associated C5a Are Essential for Assessment of C5a Generation In Vivo

Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.

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