Evidence map›Paper›PMID 27148258›Full record

ArticleFrontiers in immunology2016

NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways.

Joshua Yuen, Fred G Pluthero, David N Douda, Magdalena Riedl, Ahmed Cherry, Marina Ulanova, Walter H A Kahr, Nades Palaniyar, Christoph Licht

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 3 pooled it
6.4field-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

110 citing papers in PubMed, 3 syntheses or guidelines pooled it, 156 citations in OpenAlex.

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  20. NETosis in hypersensitivity disorders.Molecular biology reports · 2025
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50 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

9 authors at 3 institutions in 1 country.

Joshua YuenCell Biology Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Program in Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Fred G PlutheroCell Biology Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
David N DoudaProgram in Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Magdalena RiedlCell Biology Program, The Hospital for Sick Children Research Institute , Toronto, ON , Canada.
Ahmed CherryCell Biology Program, The Hospital for Sick Children Research Institute , Toronto, ON , Canada.
Marina UlanovaDivision of Medical Sciences, Northern Ontario School of Medicine, Lakehead University , Thunder Bay, ON , Canada.
Walter H A KahrCell Biology Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
Nades PalaniyarProgram in Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Christoph LichtCell Biology Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Program in Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada; Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
Hospital for Sick Children · CAUniversity of Toronto · CALakehead University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neutrophils deposit antimicrobial proteins, such as myeloperoxidase and proteases on chromatin, which they release as neutrophil extracellular traps (NETs). Neutrophils also carry key components of the complement alternative pathway (AP) such as properdin or complement factor P (CFP), complement factor B (CFB), and C3. However, the contribution of these complement components and complement activation during NET formation in the presence and absence of bacteria is poorly understood. We studied complement activation on NETs and a Gram-negative opportunistic bacterial pathogen Pseudomonas aeruginosa (PA01, PAKwt, and PAKgfp). Here, we show that anaphylatoxin C5a, formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA), which activates NADPH oxidase, induce the release of CFP, CFB, and C3 from neutrophils. In response to PMA or P. aeruginosa, neutrophils secrete CFP, deposit it on NETs and bacteria, and induce the formation of terminal complement complexes (C5b-9). A blocking anti-CFP antibody inhibited AP-mediated but not non-AP-mediated complement activation on NETs and P. aeruginosa. Therefore, NET-mediated complement activation occurs via both AP- and non AP-based mechanisms, and AP-mediated complement activation during NETosis is dependent on CFP. These findings suggest that neutrophils could use their "AP tool kit" to readily activate complement on NETs and Gram-negative bacteria, such as P. aeruginosa, whereas additional components present in the serum help to fix non-AP-mediated complement both on NETs and bacteria. This unique mechanism may play important roles in host defense and help to explain specific roles of complement activation in NET-related diseases.

Indexed as

alternative pathwaycomplement systemNETosisneutrophil extracellular trapsproperdinPseudomonas aeruginosa

Identifiers

PMID27148258
PMCPMC4831636
OpenAlexW2336592170

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.