| 1. |
- Matsui, Shinobu, et al.
(author)
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Specific removal of beta1-adrenoceptor autoantibodies by immunoabsorption in rabbits with autoimmune cardiomyopathy improved cardiac structure and function.
- 2006
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In: Journal of molecular and cellular cardiology. - : Elsevier BV. - 0022-2828. ; 41:1, s. 78-85
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Journal article (peer-reviewed)abstract
- Growing evidence suggests that the beta1-adrenoceptor-directed autoimmune mechanism may play an important role in the pathogenesis of idiopathic dilated cardiomyopathy. The aim of this study is to further study the effect of specific immunoabsorption of anti-beta1-adrenoceptor autoantibodies on cardiac structure and function in autoimmune cardiomyopathy in rabbits. Twenty-four male rabbits were divided into 2 groups: (1) one immunized with beta1-adrenoceptor peptide (beta1 group, n=16), and (2) the other receiving saline injection as a control (control group, n=8). Immunization was performed once a month for 8 months. A high concentration of anti-beta1-adrenoceptor autoantibodies was exhibited throughout the immunization period. Rabbits in the beta1 group showed increased left ventricular end-diastolic diameter (LVDd), decreased left ventricular ejection fraction (LVEF) and increased LV mass/body weight ratio after the 8th month. Immunoabsorption with beta1-adrenoceptor peptide column was able to remove up to 35% of anti-beta1-adrenoceptor autoantibodies in 2 h, resulting in decreased LVDd and increased LVEF 3 months after. Specific removal of anti-beta1-adrenoceptor autoantibodies improved cardiac structure and function in experimental autoimmune cardiomyopathy. These results suggest that anti-beta1-adrenoceptor autoantibodies are of pathogenic importance in the induction of cardiomyopathy, and that specific immunoabsorption as an emerging therapy may be considered when anti-beta1-adrenoceptor autoantibodies are pathophysiologically involved.
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| 2. |
- Matsui, Shinobu, et al.
(author)
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Transfer of immune components from rabbit autoimmune cardiomyopathy into severe combined immunodeficiency (SCID) mice induces cardiomyopathic changes.
- 2006
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In: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 39:2, s. 121-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Growing evidence suggests that autoimmune mechanism plays an important role in the pathogenesis of cardiomyopathy. The purpose of this study was to investigate whether passive transfer of IgG and/or lymphocytes from rabbits with autoimmune cardiomyopathy is able to reproduce cardiomyopathic changes in severe combined immunodeficiency (SCID) mice. METHODS AND RESULTS: SCID mice were injected intraperitoneally with IgG and/or peripheral blood lymphocytes (PBL) from either rabbits immunized with both beta1-adrenoceptor peptide and M2-muscarinic receptor peptide (beta1+M2 group) or rabbits with adjuvant (N group). Thirty five SCID mice were divided into seven groups; N-IgG, N-PBL, N-IgG & PBL, (beta1+M2)-IgG, (beta1+M2)-PBL, (beta1+M2)-IgG & PBL and control groups. Heart weight in three (beta1+M2) groups were significantly increased. All mice in three (beta1+M2) groups showed high titer of rabbit anti-beta1 adrenoceptor autoantibodies, and 4 mice in the (beta1+M2)-PBL group and 3 mice in the (beta1+M2)-IgG & PBL group showed a significant increase in titer of rabbit anti-M2-muscarinic receptor autoantibodies. Focal infiltration of inflammatory cells in the myocardium was observed in the (beta1+M2)-IgG & PBL group. In the (beta1+M2)-PBL group and (beta1+M2)-IgG & PBL group, cardiomyocyte diameters were significantly increased. Some myocytes of the (beta1+M2)-IgG & PBL group exhibited intracellular edema, clumps of Z-band and increased numbers of mitochondria by using electron microscopy. CONCLUSION: Transfer of IgG and PBL from rabbits immunized with combined beta1 and M2 peptides was able to reproduce the early stage of cardiomyopathic changes in SCID mice.
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| 3. |
- Matsui, Shinobu, et al.
(author)
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Transfer of rabbit autoimmune cardiomyopathy into severe combined immunodeficiency mice.
- 2003
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In: Journal of cardiovascular pharmacology. - 0160-2446. ; 42 Suppl 1
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Journal article (peer-reviewed)abstract
- Growing evidence suggests that the autoimmune mechanism plays an important role in the pathogenesis of dilated cardiomyopathy. The purpose of this study was to evaluate the effect on the cardiac structure and function by the transfer of immunoglobulin G (IgG) and/or lymphocytes from rabbits immunized with a synthetic peptide corresponding to the sequence of the second extracellular loop of beta1-adrenoceptor (beta peptide) into severe combined immunodeficiency (SCID) mice. CB-17 SCID mice were injected intraperitoneally with 2 mg of IgG and/or 1 x 10(7) peripheral blood lymphocytes (PBL) from either rabbits immunized with both beta1 peptide and adjuvant (beta group), and adjuvant or rabbits with adjuvant only (N group). Thirty-five SCID mice were divided into seven groups: (1) N-IgG group; (2) N-PBL group; (3) N-IgG+PBL group; (4) beta-IgG group; (5) beta-PBL group; (6) beta-IgG+PBL group; and (7) control group. Morphological, serological and endocrinological studies were performed 70 days after the transfer. Results showed that heart weight and heart weight/body weight ratio in the beta-IgG+PBL group tended to be increased as compared with those in other groups. All mice in the beta-IgG group, two in the beta-PBL group and four in the beta-IgG+PBL group showed high titer of rabbit anti-beta1-adrenoceptor antibodies. Brain natriuretic peptide in the beta-IgG+PBL group showed a significant increase as compared with those in the control group and N-IgG+PBL. Pathohistologically, focal infiltration of inflammatory cells in the myocardium was observed in one mouse of the beta-IgG+PBL group. Rabbit CD3-positive T-lymphocytes in the myocardium were observed in two mice of the beta group. In conclusion, transfer of IgG and PBL from rabbits immunized with beta1 peptide was able to induce the early stages of myocardial damage in SCID mice. These data provide direct evidence that the autoimmune mechanism is important in the pathogenesis of dilated cardiomyopathy.
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