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Classical pathway of complement activation in mammalian kidneys
J Zwirner1, E Felber, R Burger
1Institut für Immunologie, Ludwig-Maximilians-Universität München, Germany.
Immunology
|October 1, 1993
Summary
Monoclonal antibodies (mAbs) targeting the complement C4d fragment were tested against mammalian complement. These studies confirmed C4d presence in mammalian glomeruli, indicating classical pathway activation and immune complex clearance.
Area of Science:
- Immunology
- Nephrology
- Complement System
Background:
- The complement system plays a crucial role in immune responses and homeostasis.
- Complement protein C4 (C4) and its fragments, particularly C4d, are important biomarkers in various immunological and renal conditions.
- Understanding the distribution and function of C4d in mammals is essential for diagnosing and managing kidney diseases.
Purpose of the Study:
- To investigate the cross-reactivity of monoclonal antibodies (mAbs) specific for human complement C4d and C4 gamma-chain against mammalian complement proteins.
- To determine the presence and localization of C4d deposits in mammalian glomeruli.
- To elucidate the role of glomerular C4d deposition in renal homeostasis and immune complex clearance.
Main Methods:
- Development and testing of monoclonal antibodies (mAbs M4d2, M4d3, M4c3) against human complement C4d and C4 gamma-chain.
- Cross-reactivity assays using complement from various mammalian species (guinea-pig, cattle, baboon, rhesus monkey) via activation ELISA.
- Immunohistochemical staining of renal tissue sections from different mammalian species, including complement-deficient animals, to detect glomerular C4d deposits.
- Comparison of glomerular IgM deposits in normal versus complement-deficient guinea-pigs.
Main Results:
- mAbs M4d2 and M4d3 showed cross-reactivity with C4d from guinea-pig, cattle, baboon, and rhesus monkey complement.
- mAbs M4d2 and M4d3, but not M4c3, stained glomerular deposits in renal tissues of pigs, cattle, and guinea-pigs.
- Specificity of M4d2 staining was confirmed in kidney specimens from C4-deficient guinea-pigs, indicating the presence of C4d in mammalian glomeruli.
- C4-deficient and C2-deficient guinea-pigs exhibited markedly increased glomerular IgM deposits compared to normal animals.
Conclusions:
- The C4d fragment is present in mammalian glomeruli, similar to humans.
- Glomerular C4d deposition signifies activation of the complement classical pathway.
- Glomerular C4d deposition appears to be a general phenomenon in renal homeostasis and plays a role in the physiological clearance of immune complexes.
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