Decay-accelerating factor regulates complement-mediated damage in the human atherosclerotic wall.
Decay-accelerating factor (DAF) is an intrinsic membrane inhibitor that regulates the activity of C3 and C5 convertases of the classical and alternative complement pathways. Using two monoclonal antibodies, IC6 and IA10, DAF was localized by immunohistochemistry using streptavidin-biotin-peroxidase complex or silver-intensified immunogold techniques in aortic, iliac and femoral samples obtained at surgery and autopsy from 32 patients. DAF was localized on the cells and in the connective tissue matrix of the arterial wall. Fibrous plaques and intimal thickenings presented larger amounts than fatty streaks, intimae and normal areas. By Western blotting analysis, DAF extracted from the arterial wall had a molecular weight of about 67 kDa. Using a double-labeling technique, DAF and C5b-9 complexes were co-localized on nucleated cells and on cell debris. The cells isolated after enzyme digestion of the arterial wall were tested for the protective role of DAF to complement-mediated damage. When DAF of the sensitized cells was blocked by monoclonal antibodies, complement-mediated cell lysis was enhanced from 10-15% to 60-70%. The effect of anti-DAF antibodies was dose-dependent. DAF blocking in the absence of antibodies used for sensitization led to a lysis under 10%. These data suggest a protective role of DAF against autologous complement activation, however insufficient to prevent complement activation in the human atherosclerotic wall.
Niculescu
F
F
Medical Clinic No. 1, Cluj-Napoca, Roumania.
Rus
H G
HG
Vlaicu
R
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001161:Arteriosclerosis / Q000276:immunology* / Q000378:metabolism; D001808:Blood Vessels / Q000276:immunology*; D015153:Blotting, Western; D018958:CD55 Antigens; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D018958:CD55 Antigens; D015938:Complement Membrane Attack Complex; D008565:Membrane Proteins