Nicotine induces neutrophil extracellular traps.
NETs serve to ensnare and kill microbial pathogens. However, NETs can at the same time contribute to tissue damage and excessive inflammation. Nicotine is a major toxic agent and has been associated with exacerbated inflammatory diseases. The current study aimed at investigating the role of nicotine, the addictive component of tobacco and electronic cigarettes, on triggering NET formation. We report that nicotine induces neutrophils to release NETs in a dose-dependent manner. Nicotine-induced NET formation is mediated via nicotine acetylcholine receptors, depends on Akt and PAD4 activation, but is Nox2-independent, as demonstrated by pharmacological inhibition of Nox2 and by use of Nox2-deficient mouse neutrophils. These findings demonstrate that nicotine induces NETs, which may in turn contribute to smoking-related diseases.
Department of Clinical Microbiology, Umeå University, Umeå, Sweden.|Umeå Centre for Microbial Research (UCMR), Umeå, Sweden.|Laboratory for Molecular Infection Medicine, Umeå, Sweden (MIMS).
Ava
A
Hosseinzadeh
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester Massachusetts, USA.
Paul R
PR
Thompson
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA.|Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA; and.|Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
Brahm H
BH
Segal
Department of Clinical Microbiology, Umeå University, Umeå, Sweden; constantin.urban@umu.se.|Umeå Centre for Microbial Research (UCMR), Umeå, Sweden.|Laboratory for Molecular Infection Medicine, Umeå, Sweden (MIMS).
Constantin F
CF
Urban
D000818:Animals; D017209:Apoptosis; D004305:Dose-Response Relationship, Drug; D065206:Extracellular Traps / Q000187:drug effects*; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000648:ultrastructure; D009538:Nicotine / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000187:drug effects
D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D051058:Oncogene Protein v-akt; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; C552151:peptidylarginine deiminase 4, mouse
ROS; nicotinic acetylcholine receptor; protein kinase B; tobacco