Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation

Koshu Okubo, Mako Kamiya, Yasuteru Urano, Hiroshi Nishi, Jan M. Herter, Tanya Mayadas, Daigoro Hirohama, Kazuo Suzuki, Hiroshi Kawakami, Mototsugu Tanaka, Miho Kurosawa, Shinji Kagaya, Keiichi Hishikawa, Masaomi Nangaku, Toshiro Fujita, Matsuhiko Hayashi, Junichi Hirahashi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Neutrophils are central players in the innate immune system. They generate neutrophil extracellular traps (NETs), which protect against invading pathogens but are also associated with the development of autoimmune and/or inflammatory diseases and thrombosis. Here, we report that lactoferrin, one of the components of NETs, translocated from the cytoplasm to the plasma membrane and markedly suppressed NETs release. Furthermore, exogenous lactoferrin shrunk the chromatin fibers found in released NETs, without affecting the generation of oxygen radicals, but this failed after chemical removal of the positive charge of lactoferrin, suggesting that charge-charge interactions between lactoferrin and NETs were required for this function. In a model of immune complex-induced NET formation in vivo, intravenous lactoferrin injection markedly reduced the extent of NET formation. These observations suggest that lactoferrin serves as an intrinsic inhibitor of NETs release into the circulation. Thus, lactoferrin may represent a therapeutic lead for controlling NETs release in autoimmune and/or inflammatory diseases.

Original languageEnglish
Pages (from-to)204-215
Number of pages12
JournalEBioMedicine
Volume10
DOIs
Publication statusPublished - 2016 Aug 1

Fingerprint

Lactoferrin
Inflammation
Immune system
Pathogens
Cell membranes
Extracellular Traps
Antigen-Antibody Complex
Chromatin
Reactive Oxygen Species
Intravenous Injections
Immune System
Cytoplasm
Neutrophils
Thrombosis
Fibers
Cell Membrane

Keywords

  • Chromatin
  • Lactoferrin
  • Neutrophil extracellular traps (NETs)
  • Oxygen radicals

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation. / Okubo, Koshu; Kamiya, Mako; Urano, Yasuteru; Nishi, Hiroshi; Herter, Jan M.; Mayadas, Tanya; Hirohama, Daigoro; Suzuki, Kazuo; Kawakami, Hiroshi; Tanaka, Mototsugu; Kurosawa, Miho; Kagaya, Shinji; Hishikawa, Keiichi; Nangaku, Masaomi; Fujita, Toshiro; Hayashi, Matsuhiko; Hirahashi, Junichi.

In: EBioMedicine, Vol. 10, 01.08.2016, p. 204-215.

Research output: Contribution to journalArticle

Okubo, K, Kamiya, M, Urano, Y, Nishi, H, Herter, JM, Mayadas, T, Hirohama, D, Suzuki, K, Kawakami, H, Tanaka, M, Kurosawa, M, Kagaya, S, Hishikawa, K, Nangaku, M, Fujita, T, Hayashi, M & Hirahashi, J 2016, 'Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation', EBioMedicine, vol. 10, pp. 204-215. https://doi.org/10.1016/j.ebiom.2016.07.012
Okubo K, Kamiya M, Urano Y, Nishi H, Herter JM, Mayadas T et al. Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation. EBioMedicine. 2016 Aug 1;10:204-215. https://doi.org/10.1016/j.ebiom.2016.07.012
Okubo, Koshu ; Kamiya, Mako ; Urano, Yasuteru ; Nishi, Hiroshi ; Herter, Jan M. ; Mayadas, Tanya ; Hirohama, Daigoro ; Suzuki, Kazuo ; Kawakami, Hiroshi ; Tanaka, Mototsugu ; Kurosawa, Miho ; Kagaya, Shinji ; Hishikawa, Keiichi ; Nangaku, Masaomi ; Fujita, Toshiro ; Hayashi, Matsuhiko ; Hirahashi, Junichi. / Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation. In: EBioMedicine. 2016 ; Vol. 10. pp. 204-215.
@article{083147a722d14b4bbc85b6c6ee72b8f9,
title = "Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation",
abstract = "Neutrophils are central players in the innate immune system. They generate neutrophil extracellular traps (NETs), which protect against invading pathogens but are also associated with the development of autoimmune and/or inflammatory diseases and thrombosis. Here, we report that lactoferrin, one of the components of NETs, translocated from the cytoplasm to the plasma membrane and markedly suppressed NETs release. Furthermore, exogenous lactoferrin shrunk the chromatin fibers found in released NETs, without affecting the generation of oxygen radicals, but this failed after chemical removal of the positive charge of lactoferrin, suggesting that charge-charge interactions between lactoferrin and NETs were required for this function. In a model of immune complex-induced NET formation in vivo, intravenous lactoferrin injection markedly reduced the extent of NET formation. These observations suggest that lactoferrin serves as an intrinsic inhibitor of NETs release into the circulation. Thus, lactoferrin may represent a therapeutic lead for controlling NETs release in autoimmune and/or inflammatory diseases.",
keywords = "Chromatin, Lactoferrin, Neutrophil extracellular traps (NETs), Oxygen radicals",
author = "Koshu Okubo and Mako Kamiya and Yasuteru Urano and Hiroshi Nishi and Herter, {Jan M.} and Tanya Mayadas and Daigoro Hirohama and Kazuo Suzuki and Hiroshi Kawakami and Mototsugu Tanaka and Miho Kurosawa and Shinji Kagaya and Keiichi Hishikawa and Masaomi Nangaku and Toshiro Fujita and Matsuhiko Hayashi and Junichi Hirahashi",
year = "2016",
month = "8",
day = "1",
doi = "10.1016/j.ebiom.2016.07.012",
language = "English",
volume = "10",
pages = "204--215",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation

AU - Okubo, Koshu

AU - Kamiya, Mako

AU - Urano, Yasuteru

AU - Nishi, Hiroshi

AU - Herter, Jan M.

AU - Mayadas, Tanya

AU - Hirohama, Daigoro

AU - Suzuki, Kazuo

AU - Kawakami, Hiroshi

AU - Tanaka, Mototsugu

AU - Kurosawa, Miho

AU - Kagaya, Shinji

AU - Hishikawa, Keiichi

AU - Nangaku, Masaomi

AU - Fujita, Toshiro

AU - Hayashi, Matsuhiko

AU - Hirahashi, Junichi

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Neutrophils are central players in the innate immune system. They generate neutrophil extracellular traps (NETs), which protect against invading pathogens but are also associated with the development of autoimmune and/or inflammatory diseases and thrombosis. Here, we report that lactoferrin, one of the components of NETs, translocated from the cytoplasm to the plasma membrane and markedly suppressed NETs release. Furthermore, exogenous lactoferrin shrunk the chromatin fibers found in released NETs, without affecting the generation of oxygen radicals, but this failed after chemical removal of the positive charge of lactoferrin, suggesting that charge-charge interactions between lactoferrin and NETs were required for this function. In a model of immune complex-induced NET formation in vivo, intravenous lactoferrin injection markedly reduced the extent of NET formation. These observations suggest that lactoferrin serves as an intrinsic inhibitor of NETs release into the circulation. Thus, lactoferrin may represent a therapeutic lead for controlling NETs release in autoimmune and/or inflammatory diseases.

AB - Neutrophils are central players in the innate immune system. They generate neutrophil extracellular traps (NETs), which protect against invading pathogens but are also associated with the development of autoimmune and/or inflammatory diseases and thrombosis. Here, we report that lactoferrin, one of the components of NETs, translocated from the cytoplasm to the plasma membrane and markedly suppressed NETs release. Furthermore, exogenous lactoferrin shrunk the chromatin fibers found in released NETs, without affecting the generation of oxygen radicals, but this failed after chemical removal of the positive charge of lactoferrin, suggesting that charge-charge interactions between lactoferrin and NETs were required for this function. In a model of immune complex-induced NET formation in vivo, intravenous lactoferrin injection markedly reduced the extent of NET formation. These observations suggest that lactoferrin serves as an intrinsic inhibitor of NETs release into the circulation. Thus, lactoferrin may represent a therapeutic lead for controlling NETs release in autoimmune and/or inflammatory diseases.

KW - Chromatin

KW - Lactoferrin

KW - Neutrophil extracellular traps (NETs)

KW - Oxygen radicals

UR - http://www.scopus.com/inward/record.url?scp=85027932145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027932145&partnerID=8YFLogxK

U2 - 10.1016/j.ebiom.2016.07.012

DO - 10.1016/j.ebiom.2016.07.012

M3 - Article

C2 - 27453322

AN - SCOPUS:85027932145

VL - 10

SP - 204

EP - 215

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -