title: Mechanisms of complement activation by crystalline cholesterol.
abstract: The mechanism by which cholesterol crystals activate complement in human serum has been studied. Crystals treated with serum and washed with buffer contain a fixed C3/C5 convertase. Its generation is dependent on the presence of divalent cations (and of factor B). The cholesterol-fixed convertase is subject to decay and can be regenerated by factors B and D. C2 in combination with C1 is not essential but enhances the convertase formation. These findings indicate that it is predominantly the alternative C3/C5 convertase C3bBb(P) that assembles on cholesterol during exposure to human serum. By the use of different antisera and immunofluorescence a C3 fragment, probably C3b, was demonstrated on serum-treated crystals. Its fixation is resistant to washing with urea, and with buffers of differing pH: by hydroxylaminolysis the C3 fragment dissociates from the crystals. This indicates a covalent ester bond linking the labile binding site of activated C3 to the hydroxyl group of cholesterol. Cholesterol acetate does not fix C3 nor acquire a C3-cleaving activity upon contact with serum. In addition, cholesterol crystals bind factor I (C3b inactivator) and in this way may facilitate fixation and amplification of the alternative C3/C5 convertase.
authors.forename: W
authors.initials: W
authors.lastname: Vogt
authors.forename: I
authors.initials: I
authors.lastname: von Zabern
authors.forename: B
authors.initials: B
authors.lastname: Damerau
authors.forename: D
authors.initials: D
authors.lastname: Hesse
authors.forename: B
authors.initials: B
authors.lastname: Lühmann
authors.forename: R
authors.initials: R
authors.lastname: Nolte
mesh_terms: D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects*; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D017244:Complement Factor I; D003460:Crystallization; D010450:Endopeptidases / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans
chemical_list: D003180:Complement C3b Inactivator Proteins; D003179:Complement C3b; D002784:Cholesterol; D010450:Endopeptidases; D050577:Complement C3-C5 Convertases; D017244:Complement Factor I