Cargando…

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

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 fac...

Descripción completa

Detalles Bibliográficos
Autores principales: Yuen, Joshua, Pluthero, Fred G., Douda, David N., Riedl, Magdalena, Cherry, Ahmed, Ulanova, Marina, Kahr, Walter H. A., Palaniyar, Nades, Licht, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831636/
https://www.ncbi.nlm.nih.gov/pubmed/27148258
http://dx.doi.org/10.3389/fimmu.2016.00137
_version_ 1782427109676810240
author Yuen, Joshua
Pluthero, Fred G.
Douda, David N.
Riedl, Magdalena
Cherry, Ahmed
Ulanova, Marina
Kahr, Walter H. A.
Palaniyar, Nades
Licht, Christoph
author_facet Yuen, Joshua
Pluthero, Fred G.
Douda, David N.
Riedl, Magdalena
Cherry, Ahmed
Ulanova, Marina
Kahr, Walter H. A.
Palaniyar, Nades
Licht, Christoph
author_sort Yuen, Joshua
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4831636
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-48316362016-05-04 NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways Yuen, Joshua Pluthero, Fred G. Douda, David N. Riedl, Magdalena Cherry, Ahmed Ulanova, Marina Kahr, Walter H. A. Palaniyar, Nades Licht, Christoph Front Immunol Immunology 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. Frontiers Media S.A. 2016-04-14 /pmc/articles/PMC4831636/ /pubmed/27148258 http://dx.doi.org/10.3389/fimmu.2016.00137 Text en Copyright © 2016 Yuen, Pluthero, Douda, Riedl, Cherry, Ulanova, Kahr, Palaniyar and Licht. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yuen, Joshua
Pluthero, Fred G.
Douda, David N.
Riedl, Magdalena
Cherry, Ahmed
Ulanova, Marina
Kahr, Walter H. A.
Palaniyar, Nades
Licht, Christoph
NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways
title NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways
title_full NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways
title_fullStr NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways
title_full_unstemmed NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways
title_short NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways
title_sort netosing neutrophils activate complement both on their own nets and bacteria via alternative and non-alternative pathways
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831636/
https://www.ncbi.nlm.nih.gov/pubmed/27148258
http://dx.doi.org/10.3389/fimmu.2016.00137
work_keys_str_mv AT yuenjoshua netosingneutrophilsactivatecomplementbothontheirownnetsandbacteriaviaalternativeandnonalternativepathways
AT plutherofredg netosingneutrophilsactivatecomplementbothontheirownnetsandbacteriaviaalternativeandnonalternativepathways
AT doudadavidn netosingneutrophilsactivatecomplementbothontheirownnetsandbacteriaviaalternativeandnonalternativepathways
AT riedlmagdalena netosingneutrophilsactivatecomplementbothontheirownnetsandbacteriaviaalternativeandnonalternativepathways
AT cherryahmed netosingneutrophilsactivatecomplementbothontheirownnetsandbacteriaviaalternativeandnonalternativepathways
AT ulanovamarina netosingneutrophilsactivatecomplementbothontheirownnetsandbacteriaviaalternativeandnonalternativepathways
AT kahrwalterha netosingneutrophilsactivatecomplementbothontheirownnetsandbacteriaviaalternativeandnonalternativepathways
AT palaniyarnades netosingneutrophilsactivatecomplementbothontheirownnetsandbacteriaviaalternativeandnonalternativepathways
AT lichtchristoph netosingneutrophilsactivatecomplementbothontheirownnetsandbacteriaviaalternativeandnonalternativepathways