Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits

被引:141
作者
Matsui, S
Fu, MLX
Katsuda, S
Hayase, M
Yamaguchi, N
Teraoka, K
Kurihara, T
Takekoshi, N
Murakami, E
Hoebeke, J
Hjalmarson, A
机构
[1] GOTHENBURG UNIV, WALLENBERG LAB CARDIOVASC RES, S-41345 GOTHENBURG, SWEDEN
[2] KANAZAWA MED UNIV, DEPT CARDIOL, KANAZAWA, ISHIKAWA, JAPAN
[3] KANAZAWA MED UNIV, DEPT PATHOL 2, KANAZAWA, ISHIKAWA, JAPAN
[4] KANAZAWA MED UNIV, DEPT CLIN PATHOL, KANAZAWA, ISHIKAWA, JAPAN
[5] KANAZAWA MED UNIV, DEPT SEROL, KANAZAWA, ISHIKAWA, JAPAN
[6] KANAZAWA MED UNIV, MED RES INST, KANAZAWA, ISHIKAWA, JAPAN
[7] UFR SCI PHARMACEUT, EQUIPE IMMUNOL RECEPTEURS, CJF INSERM 9309 IMMUNOL MALAD INFECT, TOURS, FRANCE
关键词
beta(1)-adrenoceptor; M2-muscarinic receptor; immunogenic peptides; autoimmunity;
D O I
10.1006/jmcc.1996.0307
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
An experimental model of early-stage cardiomyopathy was created by immunizing rabbits for 1 year with synthetic peptides corresponding to the sequence of the second extracellular loop of either beta(1)-adrenoceptors or M2-muscarinic receptors. Thirty male rabbits were used and divided into three groups: a control group (n = 10), a group immunized with the peptide corresponding to the beta(1)-adrenoceptor (beta(1) group) (n=10) and a group immunized with the peptide corresponding to the M2-muscarinic receptor (M2 group) (n = 10). In the sera from both groups of immunized rabbits high-titres of anti-peptide antibodies were found throughout the study period but not in the sera from control rabbits or in the preimmune sera of immunized rabbits. No significant cross-reaction with peptides other than those used for immunization was found. The myocardial receptor density of both immunized groups displayed a strong trend toward receptor up-regulation. This was significant in the beta(1) group but not in the M2 group. Both groups of immunized rabbits displayed significantly enlarged ventricles and thinner walls, as compared with the control group. However, in contrast to the beta(1) group, which showed enlarged cavities in both left and right ventricles, the M2 group was mainly affected in the right ventricles. Moreover, morphological examinations of the hearts of rabbits from both immunized groups demonstrated focal myofibrillar lysis, loss of myofilament, mitochondrial swelling and condensation, sarcoplasmic vacuolation, deposition of dense granules in the sarcoplasm and the myofibrils. One of the six control rabbit hearts which were examined showed mild degenerative changes in the myocardium and scant mononuclear cell infiltration. However, when all the control rabbit hearts were examined by electron microscopy, no significant alterations were found. These results suggest that immunization by peptides, corresponding to the target sequences for anti-receptor autoantibodies in idiopathic dilated cardiomyopathy, induces morphological changes in the heart similar to those found in the human disease. (C) 1997 Academic Press Limited.
引用
收藏
页码:641 / 655
页数:15
相关论文
共 30 条
[1]   TYPE-SPECIFIC PROTECTIVE IMMUNITY EVOKED BY SYNTHETIC PEPTIDE OF STREPTOCOCCUS-PYOGENES M-PROTEIN [J].
BEACHEY, EH ;
SEYER, JM ;
DALE, JB ;
SIMPSON, WA ;
KANG, AH .
NATURE, 1981, 292 (5822) :457-459
[2]   DECREASED CATECHOLAMINE SENSITIVITY AND BETA-ADRENERGIC-RECEPTOR DENSITY IN FAILING HUMAN HEARTS [J].
BRISTOW, MR ;
GINSBURG, R ;
MINOBE, W ;
CUBICCIOTTI, RS ;
SAGEMAN, WS ;
LURIE, K ;
BILLINGHAM, ME ;
HARRISON, DC ;
STINSON, EB .
NEW ENGLAND JOURNAL OF MEDICINE, 1982, 307 (04) :205-211
[3]   MOLECULAR-CLONING AND SEQUENCING OF A CDNA-ENCODING A HUMAN ALPHA(1A) ADRENERGIC-RECEPTOR [J].
BRUNO, JF ;
WHITTAKER, J ;
SONG, JF ;
BERELOWITZ, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 179 (03) :1485-1490
[4]   HIGH PREVALENCE OF ANTIBODIES AGAINST BETA(1)-ADRENOCEPTORS AND BETA(2)-ADRENOCEPTORS IN PATIENTS WITH PRIMARY ELECTRICAL CARDIAC ABNORMALITIES [J].
CHIALE, PA ;
ROSENBAUM, MB ;
ELIZARI, MV ;
HJALMARSON, A ;
MAGNUSSON, Y ;
WALLUKAT, G ;
HOEBEKE, J .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1995, 26 (04) :864-869
[5]   STRUCTURE OF THE GENE FOR HUMAN BETA-2-ADRENERGIC RECEPTOR - EXPRESSION AND PROMOTER CHARACTERIZATION [J].
EMORINE, LJ ;
MARULLO, S ;
DELAVIERKLUTCHKO, C ;
KAVERI, SV ;
DURIEUTRAUTMANN, O ;
STROSBERG, AD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (20) :6995-6999
[6]   CLONING OF THE CDNA FOR THE HUMAN BETA-1-ADRENERGIC RECEPTOR [J].
FRIELLE, T ;
COLLINS, S ;
DANIEL, KW ;
CARON, MG ;
LEFKOWITZ, RJ ;
KOBILKA, BK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (22) :7920-7924
[7]   LOCALIZATION OF A FUNCTIONAL AUTOIMMUNE EPITOPE ON THE MUSCARINIC ACETYLCHOLINE RECEPTOR-2 IN PATIENTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY [J].
FU, LX ;
MAGNUSSON, Y ;
BERGH, CH ;
LILJEQVIST, JA ;
WAAGSTEIN, F ;
HJALMARSON, A ;
HOEBEKE, J .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (05) :1964-1968
[8]  
FU LXM, 1996, CLIN IMMUNOL IMMUNOP, V78, P203
[9]  
FU LXM, 1995, J MOL CELL CARDIOL, V27, P427
[10]  
FU LXM, 1994, CLIN IMMUNOL IMMUNOP, V72, P15