PMID- 27148258
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160505
LR  - 20220316
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 7
DP  - 2016
TI  - NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via 
      Alternative and Non-alternative Pathways.
PG  - 137
LID - 10.3389/fimmu.2016.00137 [doi]
LID - 137
AB  - 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.
FAU - Yuen, Joshua
AU  - Yuen J
AD  - Cell 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.
FAU - Pluthero, Fred G
AU  - Pluthero FG
AD  - Cell Biology Program, The Hospital for Sick Children Research Institute, Toronto, 
      ON, Canada; Division of Haematology/Oncology, The Hospital for Sick Children, 
      Toronto, ON, Canada.
FAU - Douda, David N
AU  - Douda DN
AD  - 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.
FAU - Riedl, Magdalena
AU  - Riedl M
AD  - Cell Biology Program, The Hospital for Sick Children Research Institute , 
      Toronto, ON , Canada.
FAU - Cherry, Ahmed
AU  - Cherry A
AD  - Cell Biology Program, The Hospital for Sick Children Research Institute , 
      Toronto, ON , Canada.
FAU - Ulanova, Marina
AU  - Ulanova M
AD  - Division of Medical Sciences, Northern Ontario School of Medicine, Lakehead 
      University , Thunder Bay, ON , Canada.
FAU - Kahr, Walter H A
AU  - Kahr WH
AD  - Cell 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.
FAU - Palaniyar, Nades
AU  - Palaniyar N
AD  - 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; Institute of Medical 
      Sciences, University of Toronto, Toronto, ON, Canada.
FAU - Licht, Christoph
AU  - Licht C
AD  - Cell 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.
LA  - eng
PT  - Journal Article
DEP - 20160414
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC4831636
OTO - NOTNLM
OT  - NETosis
OT  - Pseudomonas aeruginosa
OT  - alternative pathway
OT  - complement system
OT  - neutrophil extracellular traps
OT  - properdin
EDAT- 2016/05/06 06:00
MHDA- 2016/05/06 06:01
PMCR- 2016/01/01
CRDT- 2016/05/06 06:00
PHST- 2015/12/27 00:00 [received]
PHST- 2016/03/28 00:00 [accepted]
PHST- 2016/05/06 06:00 [entrez]
PHST- 2016/05/06 06:00 [pubmed]
PHST- 2016/05/06 06:01 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2016.00137 [doi]
PST - epublish
SO  - Front Immunol. 2016 Apr 14;7:137. doi: 10.3389/fimmu.2016.00137. eCollection 
      2016.