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Deposition of the terminal C5b-9 complement complex in infarcted areas of human myocardium
Insights
Complement C5b-9 deposits in heart cells signal myocardial infarction damage. This sensitive immunocytochemical staining method detects ischemic lesions and single cell necroses, aiding in understanding heart attack progression.
Area of Science:
- Cardiovascular Pathology
- Immunology
- Complement System
Background:
- The terminal complement complex, C5b-9, plays a role in inflammatory processes.
- Understanding complement deposition in myocardial infarction is crucial for diagnosing and treating ischemic heart disease.
Purpose of the Study:
- To investigate the presence and localization of C5b-9 deposits in human myocardial infarction tissue.
- To evaluate the utility of C5b-9 immunocytochemistry as a diagnostic marker for myocardial ischemia.
Main Methods:
- Immunocytochemistry using antibodies against C5b-9 neoantigens, C5, C8, C9, C3d, C4, S-protein, IgG, IgM, and IgA.
- Analysis of fresh-frozen and paraffin-embedded myocardial tissue from infarction patients and controls.
- Control reactions for succinic dehydrogenase activity to confirm staining selectivity.
Main Results:
- C5b-9 positivity was exclusively found in myocardial cells within infarction zones, particularly at the periphery.
- Staining intensity correlated with infarction severity, with strongest signals for anti-neoantigen antibodies.
- Complement components C5, C8, and C9 were detected, while C4 and IgA were negative, suggesting deposition primarily as membrane-damaging C5b-9 complexes.
Conclusions:
- Immunocytochemical staining for C5b-9 is a highly sensitive method for detecting ischemic myocardial lesions, including single cell necroses.
- Initial ischemia may impair myocardial cells' complement regulation, leading to C5b-9 deposition.
- C5b-9 deposition on cell membranes may contribute to myocardial cell damage and irreversible injury during infarction.
Abstract:
Poly- and monoclonal antibodies to neoantigens of the human C5b-9 complement complex, as well as polyclonal antibodies to C5, C8, and C9, were used to detect and identify C5b-9 deposits in human myocardial tissue. Immunocytochemical studies were performed on fresh-frozen autopsy material derived from patients with myocardial infarctions; in addition, in 17 of these patients, paraffin sections of formalin-fixed tissue were investigated. Sixteen autopsies from patients with noncardiac diseases were analyzed as controls. Without exception, C5b-9 positivity was registered selectively and exclusively on and in myocardial cells located within the zones of infarction. The selectivity of staining was confirmed by control reactions for succinic dehydrogenase activity performed in adjacent, respective double-stained sections. Most intensive staining with anti-neoantigen antibodies was observed in the peripheral areas of the infarctions. Weak staining for C3d, rather strong staining for C5 and C9, and intermediate staining with anti-C8 antibodies were observed in the same localizations. Stainings for C4 and IgA were negative, whereas immunocytochemical reactions for IgG and IgM revealed an irregular and very weak staining. Only very weak staining was also observed with a monoclonal antibody to complement S-protein, indicating that the terminal complement components were deposited mainly in the form of membrane-damaging C5b-9 complexes. Immunocytochemical staining for C5b-9 was found to represent a most sensitive tool for detection of ischemic myocardial lesions, permitting easy detection even of single cell necroses. As a working hypothesis, we suggest that initial ischemia may cause loss of the ability of the heart muscle cells to regulate complement turnover at the membrane level. The resulting deposition of C5b-9 on the cell membranes may contribute to functional disturbance and irreversible damage of myocardial cells during the infarction process.