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Posted: May 29, 2012
Study shows how nanometer size tiny substances present in polluted-air or smoke can trigger human diseases
(Nanowerk News) Polluted-air contains thousands of health-damaging nanometer size (~100-1000 times smaller than the width of a human hair) tiny particles. These tiny pollutants penetrate deep into the lungs and are an important factor in the development of various diseases. Car exhausts containing carbon particles, smoking and simply inhalation of dust of various origins for a long time have been recognised as risk factors causing chronic inflammation in the lungs. It has also been established by now that smoking or exposure to silica-containing dust can both trigger undesirable immune reactions in human leading to the development of the so-called autoimmune diseases, such as for example rheumatoid arthritis, affecting and frequently incapacitating millions of people worldwide. Recently, new concerns have been raised associated with the emerging products of nanotechnology which, if not handled appropriately, may contribute to generation of new types of airborne pollutants. Therefore, the importance of the identification of possible risks and hazards involved in the manufacturing, handling, use, and disposal of nanomaterials can't be overestimated.
The researchers of the Nanomedicine and Molecular Imaging team at the School of Medicine, Trinity College Dublin, Ireland led by Prof. Yuri Volkov investigated underlying mechanism how nanometer size tiny substances present in polluted-air or smoke can contribute to the development of immune related diseases. In their quest for the answer, the scientists applied a wide range of nanomaterials including ultra-fine carbon black, carbon nanotubes and silicon dioxide particles of different sizes, ranging from 20 to 400 nanometres, to human cells derived from the lining of the airway passages and to the cells of phagocytic origin, i.e. those cells which are most frequently exposed to the inhaled foreign particles or which are specialised to engulf and clean up our body from them. At the same time, collaborating researchers from the Health Effects Laboratory Division, National Institute for Occupational Safety & Health (NIOSH, Morgantown, WV, USA) have conducted the studies in mice exposed to chronic inhalation of air contaminated with single walled carbon nanotubes.
The team discovered the induction of protein citrullination, a specific biochemical change in proteins caused by the transformation of the amino acid arginine into the molecule called citrulline, in human cells and in mouse lung tissues following exposure to nanosized silica or carbon- derived nanomaterials. Human proteins which incorporate this modified amino acid as building blocks, can no longer function properly and are subject to destruction and elimination by the bodily defence system. Once programmed to get rid of citrullinated proteins, the immune system can start attacking its own tissues and organs, thereby causing the autoimmune processes which may result in rheumatoid arthritis. The result was clear and convincing: all types of nanoparticles under study were causing an identical response in human cells and in the lungs of mice.
Exposure to nanomaterials cresults in Ca2+-dependent activation of the enzyme peptidylargininedeiminases, which in turn cause citrullination of target proteins.
"The revelation of the molecular mechanism by which nanomaterials of distinct origin, morphology and physico- chemical properties can induce protein citrullination in exposed human cells and animals is a huge step forward in the understanding of an important trigger that may lead to autoimmune disease development" said one of the contributing first author Dr. Navin Kumar Verma, Postdoctoral Research Fellow in the Department of Clinical Medicine, Trinity College Dublin, Ireland.
According to the researchers, it is entirely feasible that some of the human diseases arising from an altered immune response with a previously uncertain origin may be triggered by the exposure of susceptible individuals to the ultra-small objects presented to us in the air which we breathe or smoke. Preventing or interfering with the resulting citrullination process looks therefore as a promising target for the development of future preventative and therapeutic approaches in rheumatoid arthritis and possibly other autoimmune conditions.
"In the years to come, one can expect the increasing variety of nanomaterials being introduced in everyday life and biomedical applications. Altered immune response developing as a result of human exposure to nanoparticles via the citrullination-dependent mechanism could contribute to the pathogenesis of autoimmune diseases such as rheumatoid arthritis" says Prof. Volkov. "This study addresses a serious health concern of the society", he continues. "Based on this information, it will be possible to develop both innovative etiotropic and pathogenetic approaches to autoimmune disease prevention and treatment, and to establish more comprehensive guidelines to nanomaterials-associated risk and safety assessment procedures".
This research work is part of an effort by researchers at Trinity College Dublin and NIOSH to classify the possible health and safety hazards of nanomaterials and devise techniques to detect and measure the risks.