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

41 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

Keywords

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

ASJC Scopus subject areas

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

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  • Cite this

    Okubo, K., Kamiya, M., Urano, Y., Nishi, H., Herter, J. M., 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, 10, 204-215. https://doi.org/10.1016/j.ebiom.2016.07.012