Evidence map›Paper›PMID 27453322›Full record

ArticleEBioMedicine2016

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 and 7 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.

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  19. Anticancer potential of lactoferrin: effects, drug synergy and molecular interactions.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025
    Review
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34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 2 countries.

Koshu OkuboDepartment of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Japan; Apheresis and Dialysis Center, School of Medicine, Keio University, Japan; Department of General Medicine, School of Medicine, Keio University, Japan.
Mako KamiyaLaboratory of Chemical Biology & Molecular Imaging, Graduate School of Medicine, The University of Tokyo, Japan.
Yasuteru UranoLaboratory of Chemical Biology & Molecular Imaging, Graduate School of Medicine, The University of Tokyo, Japan.
Hiroshi NishiDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, United States.
Jan M HerterDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, United States.
Tanya MayadasDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, United States.
Daigoro HirohamaDepartment of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Japan; Research Center for Advanced Science and Technology, The University of Tokyo, Japan.
Kazuo SuzukiInflammation Program, Graduate School of Medicine, Chiba University, Japan.
Hiroshi KawakamiDivision of Food and Nutrition, Graduate School of Human Sciences, Kyoritsu Women's University, Japan.
Mototsugu TanakaDepartment of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Japan.
Miho KurosawaDepartment of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Japan; Department of General Medicine, School of Medicine, Keio University, Japan.
Shinji KagayaNRL Pharma, Inc., Japan.
Keiichi HishikawaDepartment of Advanced Nephrology and Regenerative Medicine, The University of Tokyo, Japan.
Masaomi NangakuDepartment of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Japan.
Toshiro FujitaDepartment of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Japan; Research Center for Advanced Science and Technology, The University of Tokyo, Japan.
Matsuhiko HayashiApheresis and Dialysis Center, School of Medicine, Keio University, Japan; Department of General Medicine, School of Medicine, Keio University, Japan.
Junichi HirahashiDepartment of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Japan; Apheresis and Dialysis Center, School of Medicine, Keio University, Japan; Department of General Medicine, School of Medicine, Keio University, Japan. Electronic address: jhirahashi-tky@umin.ac.jp.
The University of Tokyo · JPHarvard University · USKeio University · JPBrigham and Women's Hospital · USChiba University · JPKyoritsu Women's University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Amino AcidsCell LineCell MembraneExtracellular TrapsGene SilencingHistonesHumansInflammationLactoferrinLeukocyte ElastaseNeutrophilsProtein TransportProteolysisReactive Oxygen SpeciesRNA InterferenceAmino AcidsHistonesLactoferrinLeukocyte ElastaseReactive Oxygen SpeciesChromatinLactoferrinNeutrophil extracellular traps (NETs)Oxygen radicals

Identifiers

PMID27453322
PMCPMC5006695
OpenAlexW2463305804

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.