title: Suppression of alternative complement pathway activity by radiographic contrast media.
abstract: The authors examined the effect of four different kinds of contrast media (ionic/non-ionic, monomer/dimer) on the activation of the complement (C) system (haemolytic activity and anaphylatoxin generation) in vitro. In addition, the authors compared the effect of contrast media on inulin-mediated generation of the anaphylatoxin derivative C3a des Arg in sera from urticarial reactors and their non-reacting controls. It was observed that the incubation of commercial iohexol, ioxaglate, iodixanol and meglumin amidotriz solutions in normal human serum (NHS) resulted in a dose-dependent decrease in the haemolytic activity of the alternative C pathway. Contrary to expectations the contrast media did not activate C in NHS. Instead, inulin-induced generation of C3a des Arg was inhibited by all the four contrast media. The strongest inhibitor was ioxaglate, an ionic dimer. No significant difference between the urticarial reactors and non-reactors in the inhibition of C3a des Arg generation was observed. In analyzing the mechanism of C inhibition we found that the contrast media solutions, particularly the ionic ones, prevented formation of the alternative pathway C3 convertase, C3bBb, by inhibiting the binding of factor B to surface-associated C3b molecules. The results suggest that the previously observed decrease in haemolytic C titres by contrast media is due to direct suppression of C activity rather than activation-induced consumption.
authors.affiliation: Department of Radiology, Helsinki University Central Hospital, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Mikkonen
authors.forename: T
authors.initials: T
authors.lastname: Lehto
authors.forename: V
authors.initials: V
authors.lastname: Koistinen
authors.forename: H J
authors.initials: HJ
authors.lastname: Aronen
authors.forename: L
authors.initials: L
authors.lastname: Kivisaari
authors.forename: S
authors.initials: S
authors.lastname: Meri
mesh_terms: D050577:Complement C3-C5 Convertases / Q000187:drug effects; D015926:Complement C3a / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000187:drug effects; D003179:Complement C3b / Q000187:drug effects / Q000378:metabolism; D011415:Complement Factor B / Q000187:drug effects / Q000378:metabolism; D017242:Complement Factor H / Q000187:drug effects / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D003287:Contrast Media / Q000494:pharmacology*; D003974:Diatrizoate Meglumine / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007472:Iohexol / Q000494:pharmacology; D007485:Ioxaglic Acid / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D014283:Triiodobenzoic Acids / Q000494:pharmacology
chemical_list: C493495:CFH protein, human; D003287:Contrast Media; D007166:Immunosuppressive Agents; D014283:Triiodobenzoic Acids; C044541:complement C3a, des-Arg-(77)-; D003974:Diatrizoate Meglumine; D007472:Iohexol; D015926:Complement C3a; D003179:Complement C3b; D017242:Complement Factor H; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B; C044834:iodixanol; D007485:Ioxaglic Acid