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Hyperosmolality impairs ammonia-mediated inflammation: implications for the renal medulla
E C Clark1, K A Nath, T H Hostetter
1Department of Medicine, University of Rochester School of Medicine, New York 14621.
The American Journal of Physiology
|July 1, 1992
Summary
High ammonia in the kidneys modifies complement component 3 (C3) but hyperosmolar conditions block its inflammatory functions. This suggests a protective mechanism against kidney damage from ammonia.
Area of Science:
- Renal physiology
- Immunology
- Complement system
Background:
- Ammonia is present in high concentrations in the renal medulla.
- Ammonia modifies complement component 3 (C3), activating the alternative pathway.
- Inflammation is typically absent in the renal medulla despite elevated ammonia levels.
Purpose of the Study:
- To investigate the impact of the renal medulla's hyperosmolar environment on ammonia-C3 interactions.
- To determine if hyperosmolality affects the ability of ammonia-modified C3 (NH3.C3) to cause cell injury and activate neutrophils.
Main Methods:
- Incubation of purified human C3 with ammonia and varying concentrations of urinary osmolytes, NaCl, and urea.
- Assessment of C3 thiolester bond disruption.
- Evaluation of cytolytic injury in MDCK cells.
- Measurement of neutrophil (PMN) degranulation and respiratory burst responses to NH3.C3.
Main Results:
- Ammonia disrupted the C3 thiolester bond, an effect not inhibited by urinary osmolytes.
- Hyperosmolar NaCl and urea significantly inhibited alternative pathway-mediated cytolytic injury and PMN responses to NH3.C3.
- Hyperosmolality also impaired PMN responses to non-NH3.C3 stimuli, indicating a general suppressive effect.
Conclusions:
- While ammonia can modify C3 in vitro, the hyperosmolar conditions of the renal medulla markedly impair the downstream inflammatory functions of NH3.C3.
- This suggests a mechanism by which the kidney medulla avoids inflammatory damage despite high ammonia levels.