{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T20:59:09Z","timestamp":1770411549342,"version":"3.49.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[1995,4,1]],"date-time":"1995-04-01T00:00:00Z","timestamp":796694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,28]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Many diseases associated with 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 cell-regulating functions of the 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 125I-C9 (median and range) were: plasma half-life (t1\/2) 25.9 (20.6-29.5) h, fractional catabolic rate (FCR) 5.7 (5.3-7.0)%\/h, and extravascular\/intravascular ratio (EV\/IV) 0.7 (0.6-1.1). The distribution of radiolabelled C9 amongst body tissues was similar to that observed for rabbit serum albumin (RSA). Activation of the 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 the 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, 125I-SC5b-9 disappeared rapidly from the plasma, falling by 50% in 0.7 (0.6-0.8) 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.<\/jats:p>","DOI":"10.1111\/j.1365-2249.1995.tb03601.x","type":"journal-article","created":{"date-parts":[[2010,7,26]],"date-time":"2010-07-26T17:01:43Z","timestamp":1280163703000},"page":"40-46","source":"Crossref","is-referenced-by-count":9,"title":["The kinetics and distribution of C9 and SC5b-9<i>in vivo<\/i>: effects of complement activation"],"prefix":"10.1093","volume":"100","author":[{"given":"J D","family":"GREENSTEIN","sequence":"first","affiliation":[{"name":"Department of Nephrology, Prince Henry Hospital and the University of New South Wales, Sydney, Australia"}]},{"given":"P W","family":"PEAKE","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Prince Henry Hospital and the University of New South Wales, Sydney, Australia"}]},{"given":"J A","family":"CHARLESWORTH","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Prince Henry Hospital and the University of New South Wales, Sydney, Australia"}]}],"member":"286","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"2022011517443712400_b1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj2640001","article-title":"Complement membrane attack on nucleated cells: resistance, recovery and non-lethal effects","volume":"264","author":"Morgan","year":"1989","journal-title":"Biochem J"},{"key":"2022011517443712400_b2","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.4049\/jimmunol.136.8.2999","article-title":"C5b-9 assembly: average binding of one C9 molecule to C5b-8 without poly-C9 formation generates a stable transmembrane pore","volume":"136","author":"Bhakdi","year":"1986","journal-title":"J Immunol"},{"key":"2022011517443712400_b3","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1084\/jem.156.1.268","article-title":"Molecular organisation of C9 within the membrane attack complex of complement: induction of circular C9 polymerisation by the C5b-8 assembly","volume":"156","author":"Podack","year":"1982","journal-title":"J Exp Med"},{"key":"2022011517443712400_b4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/BF01737843","article-title":"Functions and relevance of the terminal complement sequence","volume":"60","author":"Bhakdi","year":"1990","journal-title":"Blut"},{"key":"2022011517443712400_b5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1159\/000463070","article-title":"The pathobiology of the terminal complement complexes","volume":"6","author":"Dalmasso","year":"1989","journal-title":"Complement Inflamm"},{"key":"2022011517443712400_b6","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev.cb.07.110191.001423","article-title":"Structure and biological role of vitronectin","volume":"7","author":"Preissner","year":"1991","journal-title":"Ann Rev Cell Biol"},{"key":"2022011517443712400_b7","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1172\/JCI114594","article-title":"Human seminal clusterin (SP-40,40). Isolation and characterisation","volume":"85","author":"O'Bryan","year":"1990","journal-title":"J Clin Invest"},{"key":"2022011517443712400_b8","first-page":"182","article-title":"Localization of S protein and its relationship to the membrane attack complex of complement in renal tissue","volume":"127","author":"Falk","year":"1987","journal-title":"Am J Pathol"},{"key":"2022011517443712400_b9","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/j.1365-2249.1992.tb06459.x","article-title":"Clusterin in renal tissue: preferential localisation with the terminal complement complex and immunoglobulin deposits in glomeruli","volume":"88","author":"French","year":"1992","journal-title":"Clin Exp Immunol"},{"key":"2022011517443712400_b10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1365-3083.1985.tb01870.x","article-title":"Monoclonal antibodies recognizing a neoantigen of poly(C9) detect the human terminal complement complex in tissue and plasma","volume":"22","author":"Mollnes","year":"1985","journal-title":"Scand J Immunol"},{"key":"2022011517443712400_b11","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/ki.1985.214","article-title":"Complement and the direct mediation of immune glomerular injury: a new perspective","volume":"28","author":"Couser","year":"1985","journal-title":"Kidney Int"},{"key":"2022011517443712400_b12","first-page":"121","article-title":"Membrane attack complex deposition in experimental glomerular injury","volume":"120","author":"Perkinson","year":"1985","journal-title":"Am J Pathol"},{"key":"2022011517443712400_b13","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.4049\/jimmunol.124.3.1291","article-title":"The ninth component of human complement: purification and physichochemical characterisation","volume":"124","author":"Biesecker","year":"1980","journal-title":"J Immunol"},{"key":"2022011517443712400_b14","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1042\/bj1130299","article-title":"An enzymic method for trace iodination of immunoglobulins and other proteins","volume":"113","author":"Marchalonis","year":"1969","journal-title":"Biochem J"},{"key":"2022011517443712400_b15","doi-asserted-by":"crossref","first-page":"23845","DOI":"10.1016\/S0021-9258(17)31592-2","article-title":"Relative topography of biologically active domains of human vitronectin","volume":"269","author":"Morris","year":"1994","journal-title":"J Biol Chem"},{"key":"2022011517443712400_b16","first-page":"445","article-title":"Metabolism of radio-labelled C3: effects of in vivo activation in rabbits","volume":"16","author":"Charlesworth","year":"1974","journal-title":"Clin Exp Immunol"},{"issue":"Suppl.","key":"2022011517443712400_b17","first-page":"13","article-title":"Distribution and metabolism of 131I-labelled proteins in man","volume":"16","author":"Berson","year":"1957","journal-title":"Fed Proc"},{"key":"2022011517443712400_b18","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1088\/0031-9155\/2\/1\/305","article-title":"The theory of tracer experiments with 131I-labelled plasma proteins","volume":"2","author":"Mathews","year":"1957","journal-title":"Phys Med Biol"},{"key":"2022011517443712400_b19","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1042\/bj2090753","article-title":"Molecular compositon of the terminal membrane and fluid-phase C5b-9 complexes of rabbit complement. Absence of disulphide-bonded C9 dimers in the membrane complex","volume":"209","author":"Bhakdi","year":"1983","journal-title":"Biochem J"},{"key":"2022011517443712400_b20","first-page":"397","article-title":"Metabolism of human \u03b21H: studies in man and experimental animals","volume":"38","author":"Charlesworth","year":"1979","journal-title":"Clin Exp Immunol"},{"key":"2022011517443712400_b21","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1159\/000467856","article-title":"Early- and late-phase activation of complement evaluated by plasma levels of C3d,g and the terminal complement complex","volume":"2","author":"Mollnes","year":"1985","journal-title":"Complement"},{"key":"2022011517443712400_b22","first-page":"112","article-title":"In vivo clearance studies of the terminal fluid-phase complement complex in rabbits","volume":"77","author":"Hugo","year":"1989","journal-title":"Clin Exp Immunol"},{"key":"2022011517443712400_b23","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/ki.1990.36","article-title":"Fluid phase generation of terminal complement complex as a novel index of bioincompatibility","volume":"37","author":"Deppisch","year":"1990","journal-title":"Kidney Int"},{"key":"2022011517443712400_b24","doi-asserted-by":"crossref","first-page":"23076","DOI":"10.1016\/S0021-9258(18)50058-2","article-title":"Heparin-binding properties of vitronectin are linked to complex formation as illustrated by in vitro polymerization and binding to the terminal complement complex","volume":"267","author":"Hogasen","year":"1992","journal-title":"J Biol Chem"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2249.1995.tb03601.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/100\/1\/40\/42202512\/j.1365-2249.1995.tb03601.x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/100\/1\/40\/42202512\/j.1365-2249.1995.tb03601.x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T10:37:38Z","timestamp":1740307058000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/100\/1\/40\/6484030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,4]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2008,6,28]]},"published-print":{"date-parts":[[2008,6,28]]}},"URL":"https:\/\/doi.org\/10.1111\/j.1365-2249.1995.tb03601.x","relation":{},"ISSN":["1365-2249","0009-9104"],"issn-type":[{"value":"1365-2249","type":"electronic"},{"value":"0009-9104","type":"print"}],"subject":[],"published-other":{"date-parts":[[1995,4]]},"published":{"date-parts":[[1995,4]]}}}