Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment
Abstract Sepsis is a serious clinical problem. Negative regulation of innate immunity is associated with sepsis progression, but the underlying mechanisms remains unclear. Here we show that the receptor CD300f promotes disease progression in sepsis. CD300f −/− mice were protected from death after ce...
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Nature Portfolio
2017
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oai:doaj.org-article:aa59ba0107c3416ea07d058e0838adee2021-12-02T11:52:56ZDisrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment10.1038/s41598-017-04647-z2045-2322https://doaj.org/article/aa59ba0107c3416ea07d058e0838adee2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04647-zhttps://doaj.org/toc/2045-2322Abstract Sepsis is a serious clinical problem. Negative regulation of innate immunity is associated with sepsis progression, but the underlying mechanisms remains unclear. Here we show that the receptor CD300f promotes disease progression in sepsis. CD300f −/− mice were protected from death after cecal ligation and puncture (CLP), a murine model of septic peritonitis. CD300f was highly expressed in mast cells and recruited neutrophils in the peritoneal cavity. Analysis of mice (e.g., mast cell-deficient mice) receiving transplants of wild-type or CD300f −/− mast cells or neutrophils indicated that CD300f deficiency did not influence intrinsic migratory abilities of neutrophils, but enhanced neutrophil chemoattractant production (from mast cells and neutrophils) in the peritoneal cavity of CLP-operated mice, leading to robust accumulation of neutrophils which efficiently eliminated Escherichia coli. Ceramide-CD300f interaction suppressed the release of neutrophil chemoattractants from Escherichia coli-stimulated mast cells and neutrophils. Administration of the reagents that disrupted the ceramide-CD300f interaction prevented CLP-induced sepsis by stimulating neutrophil recruitment, whereas that of ceramide-containing vesicles aggravated sepsis. Extracellular concentrations of ceramides increased in the peritoneal cavity after CLP, suggesting a possible role of extracellular ceramides, CD300f ligands, in the negative-feedback suppression of innate immune responses. Thus, CD300f is an attractive target for the treatment of sepsis.Kumi IzawaAkie MaeharaMasamichi IsobeYuka YasudaMakoto UraiYasutaka HoshinoKeigo UenoToshihiro MatsukawaMariko TakahashiAyako KaitaniEmiko ShibaAyako TakamoriShino UchidaKoichiro UchidaKeiko MaedaNobuhiro NakanoYoshinori YamanishiToshihiko OkiDavid VoehringerAxel RoersSusumu NakaeJunko IshikawaYuki KinjoToshiaki ShimizuHideoki OgawaKo OkumuraToshio KitamuraJiro KitauraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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DOAJ |
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DOAJ |
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EN |
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Medicine R Science Q |
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Medicine R Science Q Kumi Izawa Akie Maehara Masamichi Isobe Yuka Yasuda Makoto Urai Yasutaka Hoshino Keigo Ueno Toshihiro Matsukawa Mariko Takahashi Ayako Kaitani Emiko Shiba Ayako Takamori Shino Uchida Koichiro Uchida Keiko Maeda Nobuhiro Nakano Yoshinori Yamanishi Toshihiko Oki David Voehringer Axel Roers Susumu Nakae Junko Ishikawa Yuki Kinjo Toshiaki Shimizu Hideoki Ogawa Ko Okumura Toshio Kitamura Jiro Kitaura Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment |
| description |
Abstract Sepsis is a serious clinical problem. Negative regulation of innate immunity is associated with sepsis progression, but the underlying mechanisms remains unclear. Here we show that the receptor CD300f promotes disease progression in sepsis. CD300f −/− mice were protected from death after cecal ligation and puncture (CLP), a murine model of septic peritonitis. CD300f was highly expressed in mast cells and recruited neutrophils in the peritoneal cavity. Analysis of mice (e.g., mast cell-deficient mice) receiving transplants of wild-type or CD300f −/− mast cells or neutrophils indicated that CD300f deficiency did not influence intrinsic migratory abilities of neutrophils, but enhanced neutrophil chemoattractant production (from mast cells and neutrophils) in the peritoneal cavity of CLP-operated mice, leading to robust accumulation of neutrophils which efficiently eliminated Escherichia coli. Ceramide-CD300f interaction suppressed the release of neutrophil chemoattractants from Escherichia coli-stimulated mast cells and neutrophils. Administration of the reagents that disrupted the ceramide-CD300f interaction prevented CLP-induced sepsis by stimulating neutrophil recruitment, whereas that of ceramide-containing vesicles aggravated sepsis. Extracellular concentrations of ceramides increased in the peritoneal cavity after CLP, suggesting a possible role of extracellular ceramides, CD300f ligands, in the negative-feedback suppression of innate immune responses. Thus, CD300f is an attractive target for the treatment of sepsis. |
| format |
article |
| author |
Kumi Izawa Akie Maehara Masamichi Isobe Yuka Yasuda Makoto Urai Yasutaka Hoshino Keigo Ueno Toshihiro Matsukawa Mariko Takahashi Ayako Kaitani Emiko Shiba Ayako Takamori Shino Uchida Koichiro Uchida Keiko Maeda Nobuhiro Nakano Yoshinori Yamanishi Toshihiko Oki David Voehringer Axel Roers Susumu Nakae Junko Ishikawa Yuki Kinjo Toshiaki Shimizu Hideoki Ogawa Ko Okumura Toshio Kitamura Jiro Kitaura |
| author_facet |
Kumi Izawa Akie Maehara Masamichi Isobe Yuka Yasuda Makoto Urai Yasutaka Hoshino Keigo Ueno Toshihiro Matsukawa Mariko Takahashi Ayako Kaitani Emiko Shiba Ayako Takamori Shino Uchida Koichiro Uchida Keiko Maeda Nobuhiro Nakano Yoshinori Yamanishi Toshihiko Oki David Voehringer Axel Roers Susumu Nakae Junko Ishikawa Yuki Kinjo Toshiaki Shimizu Hideoki Ogawa Ko Okumura Toshio Kitamura Jiro Kitaura |
| author_sort |
Kumi Izawa |
| title |
Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment |
| title_short |
Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment |
| title_full |
Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment |
| title_fullStr |
Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment |
| title_full_unstemmed |
Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment |
| title_sort |
disrupting ceramide-cd300f interaction prevents septic peritonitis by stimulating neutrophil recruitment |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/aa59ba0107c3416ea07d058e0838adee |
| work_keys_str_mv |
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