The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells

Pretreatment with synthetic C-reactive protein (CRP), a functional CRP peptide, has the potential to augment macrophage phagocytosis by bacterial challenge. However, the posttreatment is clinically ideal. We investigated the efficacy of posttreatment with synthetic CRP on murine cecal ligation and p...

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Main Authors: Manabu Kinoshita, Seigo Ito, Takuya Ishikiriyama, Kumiko Sekiguchi, Ryota Yamaguchi, Ryoichi Tsuruhara, Akihisa Matsuda, Kazuki Koiwa, Masahiro Nakashima, Hiroyuki Nakashima, Masao Miyashita, Shuhji Seki
Format: Article
Language:English
Published: Karger Publishers 2021-05-01
Series:Journal of Innate Immunity
Subjects:
Online Access:https://www.karger.com/Article/FullText/515333
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author Manabu Kinoshita
Seigo Ito
Takuya Ishikiriyama
Kumiko Sekiguchi
Ryota Yamaguchi
Ryoichi Tsuruhara
Akihisa Matsuda
Kazuki Koiwa
Masahiro Nakashima
Hiroyuki Nakashima
Masao Miyashita
Shuhji Seki
author_facet Manabu Kinoshita
Seigo Ito
Takuya Ishikiriyama
Kumiko Sekiguchi
Ryota Yamaguchi
Ryoichi Tsuruhara
Akihisa Matsuda
Kazuki Koiwa
Masahiro Nakashima
Hiroyuki Nakashima
Masao Miyashita
Shuhji Seki
author_sort Manabu Kinoshita
collection DOAJ
description Pretreatment with synthetic C-reactive protein (CRP), a functional CRP peptide, has the potential to augment macrophage phagocytosis by bacterial challenge. However, the posttreatment is clinically ideal. We investigated the efficacy of posttreatment with synthetic CRP on murine cecal ligation and puncture (CLP), focusing on liver macrophages. Mice received CLP, and 1 h later, synthetic CRP or saline was intraperitoneally administered. Posttreatment with synthetic CRP increased the murine survival after CLP. It reduced viable bacterial counts in the liver 24 h after CLP with an increase in the number of Kupffer cells but not monocyte-derived liver macrophages. Posttreatment with synthetic CRP increased the phagolytic activity of Kupffer cells against Escherichia coli (E. coli) as well as capsulated Klebsiella pneumoniae at 3 h after CLP. Synthetic CRP therapy augmented TNF production by E. coli-phagocytosing Kupffer cells, resulting in an increase in tissue TNF levels in the liver at 24 h. Kupffer cells substantially expressed FcγRI, which is a ligand of CRP, and their FcγRI expression was further increased after CLP. In contrast, synthetic CRP therapy affected neither the phagocytic function of monocyte-derived liver macrophages (showing a weak FcγRI expression) nor their TNF production. Depletion of Kupffer cells in mice inhibited these beneficial effects of synthetic CRP in CLP mice. Conclusion: Posttreatment with synthetic CRP effectively improves murine bacterial peritonitis via the activation of phagocytosis of FcγRI-expressing Kupffer cells.
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spelling doaj.art-1144cc3d5d3748deaf6beb88d59799a32022-12-21T22:02:39ZengKarger PublishersJournal of Innate Immunity1662-811X1662-81282021-05-0111310.1159/000515333515333The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer CellsManabu Kinoshita0Seigo Ito1Takuya Ishikiriyama2Kumiko Sekiguchi3Ryota Yamaguchi4Ryoichi Tsuruhara5Akihisa Matsuda6Kazuki Koiwa7Masahiro Nakashima8Hiroyuki Nakashima9Masao Miyashita10Shuhji Seki11Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, JapanDepartment of Nephrology and Endocrinology, National Defense Medical College, Tokorozawa, Saitama, JapanDepartment of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, JapanDepartment of Surgery, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, JapanMedical Student, National Defense Medical College, Tokorozawa, Saitama, JapanMedical Student, National Defense Medical College, Tokorozawa, Saitama, JapanDepartment of Surgery, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, JapanDepartment of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, JapanDepartment of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, JapanDepartment of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, JapanDepartment of Surgery, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, JapanDepartment of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, JapanPretreatment with synthetic C-reactive protein (CRP), a functional CRP peptide, has the potential to augment macrophage phagocytosis by bacterial challenge. However, the posttreatment is clinically ideal. We investigated the efficacy of posttreatment with synthetic CRP on murine cecal ligation and puncture (CLP), focusing on liver macrophages. Mice received CLP, and 1 h later, synthetic CRP or saline was intraperitoneally administered. Posttreatment with synthetic CRP increased the murine survival after CLP. It reduced viable bacterial counts in the liver 24 h after CLP with an increase in the number of Kupffer cells but not monocyte-derived liver macrophages. Posttreatment with synthetic CRP increased the phagolytic activity of Kupffer cells against Escherichia coli (E. coli) as well as capsulated Klebsiella pneumoniae at 3 h after CLP. Synthetic CRP therapy augmented TNF production by E. coli-phagocytosing Kupffer cells, resulting in an increase in tissue TNF levels in the liver at 24 h. Kupffer cells substantially expressed FcγRI, which is a ligand of CRP, and their FcγRI expression was further increased after CLP. In contrast, synthetic CRP therapy affected neither the phagocytic function of monocyte-derived liver macrophages (showing a weak FcγRI expression) nor their TNF production. Depletion of Kupffer cells in mice inhibited these beneficial effects of synthetic CRP in CLP mice. Conclusion: Posttreatment with synthetic CRP effectively improves murine bacterial peritonitis via the activation of phagocytosis of FcγRI-expressing Kupffer cells.https://www.karger.com/Article/FullText/515333cecal ligation and punctureliver macrophagesphagolysosomal activity
spellingShingle Manabu Kinoshita
Seigo Ito
Takuya Ishikiriyama
Kumiko Sekiguchi
Ryota Yamaguchi
Ryoichi Tsuruhara
Akihisa Matsuda
Kazuki Koiwa
Masahiro Nakashima
Hiroyuki Nakashima
Masao Miyashita
Shuhji Seki
The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells
Journal of Innate Immunity
cecal ligation and puncture
liver macrophages
phagolysosomal activity
title The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells
title_full The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells
title_fullStr The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells
title_full_unstemmed The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells
title_short The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells
title_sort efficacy of posttreatment with synthetic c reactive protein in murine bacterial peritonitis via activation of fcγri expressing kupffer cells
topic cecal ligation and puncture
liver macrophages
phagolysosomal activity
url https://www.karger.com/Article/FullText/515333
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