Intravital Imaging of Neutrophil Recruitment Reveals the Efficacy of FPR1 Blockade in Hepatic Ischemia-Reperfusion Injury
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- Masaki Honda
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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- Takayuki Takeichi
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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- Shintaro Hashimoto
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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- Daiki Yoshii
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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- Kaori Isono
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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- Shintaro Hayashida
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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- Yuki Ohya
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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- Hidekazu Yamamoto
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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- Yasuhiko Sugawara
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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- Yukihiro Inomata
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Abstract
<jats:title>Abstract</jats:title> <jats:p>Neutrophils are considered responsible for the pathophysiological changes resulting from hepatic ischemia-reperfusion (I/R) injury, which is a complication of trauma, shock, liver resection, and transplantation. Recently, evidence is accumulating that formyl-peptide receptor (FPR) signaling constitutes an important danger signal that guides neutrophils to sites of inflammation. This study aimed to investigate dynamic neutrophil recruitment using two-photon laser-scanning microscopy (TPLSM) in response to FPR1 blockade during hepatic I/R. LysM-eGFP mice were subjected to partial warm hepatic I/R. They were pretreated with an FPR1 antagonist, cyclosporine H (CsH), or formyl peptide, fMLF. Liver was imaged after hepatic laser irradiation or I/R using the TPLSM technique. CsH treatment alleviated hepatic I/R injury, as evidenced by decreased serum transaminase levels, reduced hepatocyte necrosis/apoptosis, and diminished inflammatory cytokine, chemokine, and oxidative stress. In contrast, systemic administration of fMLF showed few effects. Time-lapse TPLSM showed that FPR1 blockade inhibited the accumulation of neutrophils in the necrotic area induced by laser irradiation in vivo. In the CsH-treated I/R group, the number and crawling velocity of neutrophils in the nonperfused area were lower than those in the control group. Meanwhile, FPR1 blockade did not affect monocyte/macrophage recruitment. Hepatic I/R promoted the retention of neutrophils and their active behavior in the spleen, whereas CsH treatment prevented their changes. Intravital TPLSM revealed that formyl-peptide–FPR1 signaling is responsible for regulating neutrophil chemotaxis to allow migration into the necrotic area in hepatic I/R. Our findings suggest effective approaches for elucidating the mechanisms of immune cell responses in hepatic I/R.</jats:p>
Journal
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- The Journal of Immunology
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The Journal of Immunology 198 (4), 1718-1728, 2017-02-15
The American Association of Immunologists
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Keywords
Details 詳細情報について
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- CRID
- 1363107369651281664
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- ISSN
- 15506606
- 00221767
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- Data Source
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- Crossref