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Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition
Winston L Hutchinson1, Jeff Herbert, Marina Botto
1Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London, UK.
Immunology
|May 19, 2004
Summary
Complement activation is not required for the development of amyloid A (AA) amyloidosis in mice. This finding challenges the role of the complement system in the early stages of this inflammatory disease.
Area of Science:
- Immunology
- Pathology
- Complement System Biology
Background:
- Reactive systemic amyloid A protein (AA) amyloidosis is characterized by amyloid deposits, primarily in the spleen.
- The localization of immune complexes and the scrapie agent in the spleen is complement-dependent.
- The role of the complement system in AA amyloid deposition remained unclear.
Purpose of the Study:
- To investigate the potential involvement of the complement system in the experimental induction of AA amyloidosis.
- To determine if complement activation is necessary for the early deposition of AA amyloid in the spleen.
Main Methods:
- Induction of AA amyloidosis in mice using chronic or acute inflammation.
- Depletion of circulating C3 using cobra venom factor.
- Analysis of AA amyloid deposition in mice with targeted gene deletions for complement components (C1q, factor B, C2).
Main Results:
- Depletion of C3 had minimal impact on experimental amyloid deposition.
- Mice lacking C1q or both factor B and C2 exhibited AA amyloid deposition comparable to wild-type controls.
- Complement activation via classical or alternative pathways was not essential for AA amyloid induction.
Conclusions:
- Complement activation is not a prerequisite for the experimental induction of systemic AA amyloidosis in mice.
- The findings suggest that pathways other than complement activation mediate the initial deposition of AA amyloid in the spleen.