Complement components, but not complement inhibitors, are upregulated in atherosclerotic plaques.
Complement activation occurs in atherosclerotic plaques. The capacity of arterial tissue to inhibit this activation through generation of the complement regulators C1 inhibitor, decay accelerating factor, membrane cofactor protein (CD46), C4 binding protein (C4BP), and protectin (CD59) was evaluated in pairs of aortic atherosclerotic plaques and nearby normal artery from 11 human postmortem specimens. All 22 samples produced mRNAs for each of these proteins. The ratios of plaque versus normal artery pairs was not significantly different from unity for any of these inhibitors. However, in plaques, the mRNAs for C1r and C1s, the substrates for the C1 inhibitor, were increased 2.35- and 4.96-fold, respectively, compared with normal artery; mRNA for C4, the target for C4BP, was elevated l.34-fold; and mRNAs for C7 and C8, the targets for CD59, were elevated 2.61- and 3.25-fold, respectively. By Western blotting and immunohistochemistry, fraction Bb of factor B, a marker of alternative pathway activation, was barely detectable in plaque and normal arterial tissue. These data indicate that it is primarily the classical, not the alternative pathway, that is activated in plaques and that key inhibitors are not upregulated to defend against this activation.
Yasojima
K
K
Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver.
Schwab
C
C
McGeer
E G
EG
McGeer
P L
PL
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D001011:Aorta / Q000276:immunology; D001158:Arteries / Q000276:immunology; D001161:Arteriosclerosis / Q000276:immunology*; D018958:CD55 Antigens / Q000096:biosynthesis / Q000235:genetics; D018957:CD59 Antigens / Q000096:biosynthesis / Q000235:genetics; D003167:Complement Activation; D003172:Complement C1 / Q000096:biosynthesis / Q000235:genetics; D003174:Complement C1 Inactivator Proteins / Q000096:biosynthesis / Q000235:genetics; D050718:Complement C1 Inhibitor Protein; D003181:Complement C4 / Q000096:biosynthesis / Q000235:genetics; D003184:Complement C7 / Q000096:biosynthesis / Q000235:genetics; D003185:Complement C8 / Q000096:biosynthesis / Q000235:genetics; D003169:Complement Inactivator Proteins / Q000096:biosynthesis* / Q000235:genetics; D003165:Complement System Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis / Q000235:genetics; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D003181:Complement C4; D003184:Complement C7; D003185:Complement C8; D003169:Complement Inactivator Proteins; D016167:Integrin alphaXbeta2; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D003165:Complement System Proteins