title: Efficient amyloid A clearance in the absence of immunoglobulins and complement factors.
abstract: Amyloid A amyloidosis is a protein misfolding disease characterized by deposition of extracellular aggregates derived from the acute-phase reactant serum amyloid A protein. If untreated, amyloid A amyloidosis leads to irreversible damage of various organs, including the kidneys, liver, and heart. Amyloid A deposits regress upon reduction of serum amyloid A concentration, indicating that the amyloid can be efficiently cleared by natural mechanisms. Clearance was proposed to be mediated by humoral immune responses to amyloid. Here, we report that amyloid clearance in mice lacking complement factors 3 and 4 (C3C4(-/-)) was equally efficient as in wild-type mice (C57BL/6), and was only slightly delayed in agammaglobulinemic mice (J(H-/-)). Hence, antibodies or complement factors are not necessary for natural amyloid clearance, implying the existence of alternative physiological pathways for amyloid removal.
authors: Institute of Neuropathology, University Hospital of Zurich, 8091 Zurich, Switzerland. jana.sponarova@gmail.com
authors: Jana
authors: J
authors: Sponarova
authors: Mario
authors: M
authors: Nuvolone
authors: Charlotte
authors: C
authors: Whicher
authors: Nathalie
authors: N
authors: Frei
authors: Veronika
authors: V
authors: Kana
authors: Petra
authors: P
authors: Schwarz
authors: Gunilla T
authors: GT
authors: Westermark
authors: Adriano
authors: A
authors: Aguzzi
mesh_terms: D000361:Agammaglobulinemia / Q000378:metabolism / Q000473:pathology; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D018450:Disease Progression; D004705:Endocytosis / Q000187:drug effects; D019286:Endopeptidase K / Q000494:pharmacology; D007136:Immunoglobulins / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000954:Antigens, Surface; D007136:Immunoglobulins; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D000685:Serum Amyloid A Protein; D003165:Complement System Proteins; D019286:Endopeptidase K