Abstract: PO0392
Acetylcholine Receptor Agonist Reduces Acute Lung Injury After Renal Ischemia-Reperfusion Injury by Acting on Splenic Macrophages
Session Information
- AKI: Repair and Progression
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Goto, Daiki, Hamamatsu Ika Daigaku, Hamamatsu, Shizuoka, Japan
- Nagata, Soichiro, Hamamatsu Ika Daigaku, Hamamatsu, Shizuoka, Japan
- Naito, Yoshitaka, Hamamatsu Ika Daigaku, Hamamatsu, Shizuoka, Japan
- Iwakura, Takamasa, Hamamatsu Ika Daigaku, Hamamatsu, Shizuoka, Japan
- Isobe, Shinsuke, Hamamatsu Ika Daigaku, Hamamatsu, Shizuoka, Japan
- Fujikura, Tomoyuki, Hamamatsu Ika Daigaku, Hamamatsu, Shizuoka, Japan
- Ohashi, Naro, Hamamatsu Ika Daigaku, Hamamatsu, Shizuoka, Japan
- Kato, Akihiko, Hamamatsu Ika Daigaku, Hamamatsu, Shizuoka, Japan
- Yasuda, Hideo, Hamamatsu Ika Daigaku, Hamamatsu, Shizuoka, Japan
Group or Team Name
- First Department of Medicine
Background
Acute kidney injury (AKI) has been reported to contribute to development of acute lung injury (ALI) via proinflammatory response. Although the inflammation caused by AKI directly might affect the lungs, this inflammation has been exacerbated by splenectomy. Macrophages with α7 nicotinic acetylcholine receptor(α7nAChR), which play a central role in the cholinergic anti-inflammatory pathway (CAP), are abundant in the lung and spleen. We hypothesized that CAP could reduce ALI after AKI. The objectives of this study were to determine 1) whether AChR agonist could reduce ALI after AKI, and 2) which macrophages in the lung or spleen, could contribute to the improvement of ALI by AChR agonist.
Methods
AKI was induced in C57BL/6 male mice by unilateral ischemia-reperfusion injury (IRI) with contralateral nephrectomy. The α7nAChR selective agonist, GTS-21 was administered in three experimental settings: 1) splenectomy, 2)splenic macrophage deletion via intravenous administration of clodronate liposomes, 3)alveolar macrophage deletion via intratracheal administration of clodronate liposomes. The lung neutrophil infiltration and evans blue dye(EBD) leakage were assessed as lung injuries.
Results
GTS-21 significantly reduced lung neutrophil infiltration (23.04±3.30 vs 11.69±2.38/HPF, p<0.0001) and EBD vascular leakage(13.54±5.32 vs 8.04±3.25μg/g lung tissue, p<0.01) after renal IRI. In splenectomized mice, GTS-21 did not reduce lung injuries after renal IRI. (neutrophil infiltration: 46.39±16.65 vs 37.54±12.91/HPF, p=ns, EBD vascular leakage: 23.30±8.88 vs 22.18±10.41μg/g lung tissue p=ns). In mice depleted of splenic macrophages, GTS-21 did not reduced lung injuries after renal IRI(neutrophile infiltration: 37.03±10.54 vs 34.36±11.61/HPF, p=ns, EBD vascular leakage: 34.78±20.55 vs 49.92±39.83μg/g lung tissue, p=ns). In mice depleted of alveolar macrophages, GTS-21 significantly reduced lung injuries after IRI (neutrophil infiltration: 21.00±7.52 vs 12.93±3.64/HPF, p<0.05, EBD vascular leakage: 13.86±4.59 vs 9.74±2.25μg/g lung tissue, p<0.05).
Conclusion
AChR agonist reduces acute lung injury after renal IRI by acting on splenic macrophages.