Abstract: TH-PO846
Apoptosis Inhibitor of Macrophage Ameliorates Fungus-Induced Peritoneal Injury Model in Mice
Session Information
- Peritoneal Dialysis - I
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Dialysis
- 608 Peritoneal Dialysis
Authors
- Ito, Yasuhiko, Aichi Medical University, Nagakute, Japan
- Tomita, Takako, Nagoya Univeristy Graduate School of Medicine, Nagoya, Japan
- Mizuno, Masashi, Nagoya Univeristy Graduate School of Medicine, Nagoya, Japan
- Suzuki, Yasuhiro, Nagoya Univeristy Graduate School of Medicine, Nagoya, Japan
- Sakata, Fumiko, Nagoya Univeristy Graduate School of Medicine, Nagoya, Japan
- Takei, Yoshifumi, Aichi Gakuin University, Nagoya, Japan
- Maruyama, Shoichi, Nagoya Univeristy Graduate School of Medicine, Nagoya, Japan
Background
Fungal peritonitis is not common, but carries a most serious and poor prognosis due to severe inflammation. In addition, a single episode of fungal peritonitis can reportedly induce encapsulating peritoneal sclerosis. A decrease in the clearance of debris, such as that of apoptotic or necrotic cells, has been reported to prevent resolution of inflammation and tissue remodeling, leading to fibrosis and organ dysfunction. Recently, apoptosis inhibitor of macrophage (AIM/CD5L) was reported to enhance the phagocytic removal of debris by epithelial cells, contributing to kidney tissue repair. In this study, we investigated the roles of AIM in zymosan-induced fungal peritonitis models (zymosan models) that we previously reported (J Immunol 2009).
Methods
We studied zymosan models in wild and AIM deficient mice and evaluated the effects of recombinant AIM (rAIM) in AIM deficient zymosan models. We investigated whether rAIM enhances engulfment of cell debris by cultured macrophages and mesothelial cells.
Results
Inflammation with necrosis was much more severe in the AIM deficient mice at 4 weeks. M1 macrophages and neutrophils were predominant on days 7 and 14. M2 macrophages were higher in wild mice than in AIM deficient mice on days 21 and 28. IL-6, TNF-a, iNOS, and CD86 mRNA expression was significantly higher on day 28 in AIM deficient mice compared with wild mice. AIM levels in serum increased and peaked on day 14, and AIM was strongly detected in the necrotic area in zymosan models of wild mice on day 14. Inflammation with necrosis was suppressed by administration of rAIM in AIM deficient mice on day 28. In vitro, AIM enhanced the engulfment of necrotic debris by macrophages derived from zymosan-induced peritonitis, M1- and M2a-like bone marrow derived macrophages, as well as by mesothelial cells.
Conclusion
AIM was found to play a role in the reduction of inflammation by clearance of necrotic debris in zymosan-induced peritonitis models. Enhancement of engulfment could be a novel therapeutic strategy for improving fungal peritonitis-induced peritoneal membrane injury and prognosis.
Funding
- Government Support - Non-U.S.