title: Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition in mice.
abstract: During induction of reactive systemic amyloid A protein (AA) amyloidosis in mice, either by chronic inflammation or by severe acute inflammation following injection of amyloid enhancing factor, the earliest deposits form in a perifollicular distribution in the spleen. Because the splenic follicular localization of immune complexes and of the scrapie agent are both complement dependent in mice, we investigated the possible complement dependence of AA amyloid deposition. In preliminary experiments, substantial depletion of circulating C3 by cobra venom factor had little effect on experimental amyloid deposition. More importantly, mice with targeted deletion of the genes for C1q or for both factor B and C2, and therefore unable to sustain activation, respectively, of either the classical complement pathway or both the classical and alternative pathways, showed amyloid deposition similar to wild type controls. Complement activation by either the classical or alternative pathways is thus not apparently necessary for the experimental induction of systemic AA amyloid in mice.
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London, UK.
authors.forename: Winston L
authors.initials: WL
authors.lastname: Hutchinson
authors.forename: Jeff
authors.initials: J
authors.lastname: Herbert
authors.forename: Marina
authors.initials: M
authors.lastname: Botto
authors.forename: Mark B
authors.initials: MB
authors.lastname: Pepys
mesh_terms: D000686:Amyloidosis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015922:Complement C1q / Q000235:genetics / Q000276:immunology; D003175:Complement C2 / Q000235:genetics / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D011415:Complement Factor B / Q000235:genetics / Q000276:immunology; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D004546:Elapid Venoms; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D000685:Serum Amyloid A Protein / Q000378:metabolism*
chemical_list: D003175:Complement C2; D003176:Complement C3; D004546:Elapid Venoms; D000685:Serum Amyloid A Protein; C016310:cobra venom factor; D015922:Complement C1q; D011415:Complement Factor B