[2016-09-02] An Umeå-based team in collaboration with US researchers reveals a new link between nicotine and inflammation. They report that nicotine strongly activates immune cells to release DNA fibres decorated with pro-inflammatory molecules, so called neutrophil extracellular traps (NETs). The continuous exposure to these NETs can harm the tissue and could explain the hazardous consequences of tobacco consumption for human health.
Tobacco use causes death of nearly six m illion people annually according to WHO. Nicotine is the major addictive and toxic component in tobacco products. In cells, nicotine signals via nicotine acetylcholine receptors to mediate dangerous effects on the consumer’s body. Nicotine is a major cause of inflammatory diseases among smokers and also non-smokers by passive inhalation, such as for instance chronic obstructive lung disease (COPD). COPD is widely spread and affects more than 10% of the adult population in westernised countries. The molecular mechanisms underlying this inflammatory activity of nicotine is not well understood.
In a recently published article in the Journal of Leukocyte Biology, researchers at the Laboratory for Molecular Infection Medicine Sweden (MIMS) at Umeå University reveal a novel link between nicotine and inflammation. They found that nicotine activates neutrophils, in an undesirable fashion. Neutrophils are the most abundant type of white blood cells that circulate in the blood stream ready to attack invading microbes with an arsenal of antimicrobial compounds. Neutrophils are essential to prevent infection by engulfing invading microbes, or by releasing reactive oxygen species as well as DNA fibres from their own nuclei, termed neutrophil extracellular traps (NETs). NET release is a mixed blessing. Loaded with antimicrobial enzymes and pro-inflammatory molecules NETs are harmful to invading microbes, however, they can also potently harm the host’s own tissue, if not controlled in the right manner. In recent years, NETs have been attributed to be mediators of tissue damage in several inflammatory diseases, such as for instance small vessel vasculitis, arthritis and cancer.
For the first time, Ava Hosseinzadeh and colleagues show that nicotine triggers NET release. The signal to trigger NETs is mediated by a specific acetylcholine receptor found on neutrophils and further signalled into the cell via a protein kinase known as Akt.
“This particular finding explains the missing piece of the puzzle of tobacco usage and inflammation,” says Ava Hosseinzadeh, who worked on this project during her doctoral dissertation.
“The next evident step is to demonstrate the NET-inducing capacity of nicotine in animal models and human samples. Such ‘in vivo’ studies will enable us to attract new funders and potentially interest of the pharma industry. Our finding could hopefully lead to novel anti-inflammatory therapies of tobacco usage related diseases,” says Constantin Urban, associate professor and project leader at Umeå University.
This novel finding opens new avenues to understand the consequences of tobacco usage for human health and should be seen as one more convincing argument to quit nicotine usage in any form. Remember: Nicotine consumption causes continuous collateral damage on your tissue by unleashing NETs.
This study has been recently published in the renowned scientific magazine “Journal of Leukocyte Biology http://www.jleukbio.org/content/early/2016/06/12/jlb.3AB0815-379RR.
About the publication:
Journal of Leukocyte Biology, article: Nicotine induces neutrophil extracellular traps. Authors: Ava Hosseinzadeh, Paul R. Thompson, Brahm H. Segal and Constantin F. Urban. DOI: 10.1189/jlb.3AB0815-379RR.
For more information please contact:
Constantin Urban, Department of Clinical Microbiology at Umeå University
mobile:+46 76 209 74 05
The image illustrates how smoke from a cigarette transforms to neutrophil extracellular traps (NETs) which eventually reach blood vessels (upper red part in the image). The fibril meshwork depicted in red is taken from a microscopic image of activated neutrophils that have released NETs. Each fibre is one or more strands of DNA that is loaded with antimicrobial enzymes and inflammatory molecules. Credit: Ava Hosseinzadeh.
(Text: Constantin Urban/Anna Lawrence)