Apoptosis inhibitor of macrophage ameliorates fungus-induced peritoneal injury model in mice.

Abstract

Fungal peritonitis in a patient on peritoneal dialysis (PD) is a refractory injury accompanied by severe inflammation, predisposing patients to a poor prognosis. Defective clearance of necrotic tissue interferes with amelioration of tissue injury and induces abnormal tissue remodeling. In the recent reports, apoptosis inhibitor of macrophage (AIM, also called CD5L) prevents obesity, hepatocellular carcinoma and acute kidney injury. Here, we investigated potential roles of AIM in prevention of progression of fungal peritonitis models. AIM -/- mice subjected to zymosan-induced peritonitis exhibited progressive inflammation and sustained peritoneal necrosis tissue on day 28 after the disease induction, whereas there was an improvement in AIM +/+ mice. This appeared to be caused by deposition of AIM at the necrotic peritoneum in AIM +/+ mice. 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. In addition, administration of recombinant AIM dramatically ameliorated severe inflammation associated with necrosis in zymosan-induced peritonitis of AIM -/- mice. Our observations suggest that AIM appears to be involved in the repair process of zymosan-induced peritonitis, and thus, could be the basis of development of new therapeutic strategies for PD-related fungal peritonitis.

• Authors: Takako Tomita, Satoko Arai, Kento Kitada, Masashi Mizuno, Yasuhiro Suzuki, Fumiko Sakata, Daisuke Nakano, Emiri Hiramoto, Yoshifumi Takei, Shoichi Maruyama, Akira Nishiyama, Seiichi Matsuo, Toru Miyazaki, Yasuhiko Ito
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 6450 (07 25 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28743989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• Biomarkers
• CD5L protein, human
• Cd5l protein, mouse
• Receptors, Immunologic
• Receptors, Scavenger
• Recombinant Proteins
• Scavenger Receptors, Class B
• Zymosan

Topics

• Animals
• Apoptosis Regulatory Proteins (genetics, metabolism, pharmacology)
• Biomarkers (analysis)
• Complement Activation
• Disease Models, Animal
• Epithelial Cells (metabolism)
• Humans
• Macrophages (metabolism, pathology)
• Mice, Mutant Strains
• Peritoneal Dialysis (adverse effects)
• Peritoneum (pathology)
• Peritonitis (chemically induced, microbiology, therapy)
• Phagocytosis
• Receptors, Immunologic (genetics, metabolism)
• Receptors, Scavenger
• Recombinant Proteins (genetics, pharmacology)
• Scavenger Receptors, Class B (blood)
• Zymosan (toxicity)