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The local production of complement in the pathogenesis of renal inflammation
1Department of Nephrology and Transplantation, Guy's Hospital Medical and Dental School, King's College, London.
Insights
Local complement synthesis in the kidney may contribute to renal injury in immune-mediated glomerular diseases. This review examines evidence suggesting the kidney produces complement components, impacting kidney disease pathogenesis.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Complement deposition is characteristic of immune-mediated glomerular diseases.
- Complement activation in the glomerulus plays a pathogenic role in glomerulonephritis.
- Traditionally, deposited complement components were thought to originate from systemic circulation.
Purpose of the Study:
- To review experimental evidence regarding the local production of complement components within the kidney.
- To explore the potential pathogenic role of local complement synthesis in renal injury.
- To discuss the implications of local complement production in various kidney diseases.
Main Methods:
- Review of in vitro studies demonstrating complement production by glomerular, tubular, and inflammatory cells.
- Analysis of human biopsy data showing increased complement gene expression in inflammatory renal disease.
- Examination of experimental models of glomerulonephritis.
Main Results:
- Kidney cells (glomerular, tubular, inflammatory) can produce complement components.
- Increased complement gene expression in human kidney biopsies during inflammation suggests local synthesis.
- Experimental models indicate a pathogenic role for complement activation in the glomerulus.
Conclusions:
- Local complement synthesis is a plausible source of complement components in the kidney.
- Evidence suggests local complement production may contribute to renal injury in various glomerular diseases.
- Further direct evidence is needed to confirm the pathogenic role of local complement synthesis.
Abstract:
The deposition of complement components is a feature of many immune mediated human glomerular diseases. Experimental models provide evidence that complement activation within the glomerulus has a pathogenic role in immune complex and antibody mediated glomerulonephritis. It was thought that the complement components deposited within the kidney were derived from the systemic circulating pool. However, recent work has shown that the kidney is able to produce many of the components of the complement cascade. In vitro work has shown that cells of glomerular and tubular origin can produce complement, as can inflammatory cells present within the kidney during inflammation. Analysis of human biopsy material has shown that expression of complement genes is increased during inflammatory renal disease implicating local complement synthesis as a potential source of complement components. At present no direct evidence for a pathogenic role of local complement synthesis exists. In this review we consider the current experimental evidence which suggests that local production of complement may be contributing to renal injury in a variety of diseases.