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CD59 protects rat kidney from complement mediated injury in collaboration with crry
M Watanabe1, Y Morita, M Mizuno
1Internal Medicine III, Nagoya University School of Medicine, Nagoya, Japan.
Kidney International
|September 30, 2000
Summary
Complement regulator CD59 (cell differentiation 59) works with Crry/p65 to protect rat kidneys from complement-mediated damage. Suppressing CD59 worsens kidney injury when complement is activated at the C3 level.
Area of Science:
- Nephrology
- Immunology
- Complement System
Background:
- Crry/p65 regulates complement at the C3 level and is vital for kidney integrity.
- The role of CD59, a complement regulator at the C8/9 level, remains unclear, particularly during C3 activation.
Purpose of the Study:
- To investigate the in vivo function of CD59 in protecting the kidney under conditions of complement activation at the C3 level.
Main Methods:
- Monoclonal antibodies 5I2 and 6D1 were used to inhibit Crry and CD59, respectively.
- Rat kidneys were perfused and recirculated with antibodies to activate the alternative complement pathway.
Main Results:
- Inhibition of Crry (5I2) led to C3 and membrane attack complex (MAC) deposition, causing tubulointerstitial injury that resolved by day 7.
- Further inhibition of CD59 (6D1) exacerbated MAC deposition and worsened kidney injury in a dose-dependent manner.
- CD59 inhibition alone did not cause damage or MAC deposition.
Conclusions:
- CD59 collaborates with Crry to maintain kidney integrity against complement-mediated damage in vivo.
- CD59 plays a crucial protective role in the kidney, especially when complement is activated at the C3 level.