| Autor: |
Suguru Saito, Narihito Tatsumoto, Duo-Yao Cao, Nobuyuki Nosaka, Hiroshi Nishi, Daniel N. Leal, Ellen Bernstein, Kenichi Shimada, Moshe Arditi, Kenneth E. Bernstein, Michifumi Yamashita |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
American journal of physiology. Renal physiology. 323(4) |
| ISSN: |
1522-1466 |
| Popis: |
While angiotensin-converting enzyme (ACE) regulates blood pressure by producing angiotensin II as part of the renin-angiotensin system, we recently reported that elevated ACE in neutrophils promotes an effective immune response and increases resistance to infection. Here, we investigate if such neutrophils protect against renal injury in immune complex (IC)-mediated crescentic glomerulonephritis (GN) through complement. Nephrotoxic serum nephritis (NTN) was induced in wild-type and NeuACE mice that overexpress ACE in neutrophils. Glomerular injury of NTN in NeuACE mice was attenuated with much less proteinuria, milder histological injury, and reduced IC deposits, but presented with more glomerular neutrophils in the early stage of the disease. There were no significant defects in T and B cell functions in NeuACE mice. NeuACE neutrophils exhibited enhanced IC uptake with elevated surface expression of FcγRII/III and complement receptor CR1/2. IC uptake in neutrophils was enhanced by NeuACE serum containing elevated complement C3b. Given no significant complement activation by ACE, this suggests that neutrophil ACE indirectly preactivates C3 and that the C3b-CR1/2 axis and elevated FcγRII/III play a central role in IC elimination by neutrophils, resulting in reduced glomerular injury. The present study identified a novel renoprotective role of ACE in glomerulonephritis; elevated neutrophilic ACE promotes elimination of locally formed ICs in glomeruli via C3b-CR1/2 and FcγRII/III, ameliorating glomerular injury. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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