The scientists also discovered that the severity of the injury depends on the genetic make-up of the affected individual.
"We gained insight into why some people can remain relatively healthy in polluted areas and why others don't," said lead author Wolfgang Liedtke, M.D., Ph.D., assistant professor in the Duke Department of Medicine and an attending physician in the Duke Clinics for Pain and Palliative Care.
The work was published on-line in the journal Environmental Health Perspectives on Jan. 18.
Diesel exhaust particles, a major part of urban smog, consist of a carbon core coated with organic chemicals and metals. The Duke team showed that the particle core delivers these organic chemicals onto brush-like surfaces called cilia, which clear mucus from the airway lining.
Contact with these chemicals then triggers a "signaling cascade," as the cells respond.
In some patients, who have a single "letter" difference in their DNA, a circuit called the TRPV4 ion channel signals more strongly in response to the pollutants. Previous research showed that this gene variant makes humans more liable to develop chronic-obstructive disease (COPD), and the current study provides an explanation for this observation.
About 75 percent of people have the version of the gene MMP-1 that leads to greater production of the molecule MMP-1 mediator, which destroys lung tissue. This genetic make-up allows for a turbo-charged production of MMP-1, which damages airways and lungs at multiple levels, Liedtke said.
A more fortunate 25 percent of people escape this high level of production of MMP-1, which may be reflected in the fact that certain individuals can better manage the effects of air pollution without grave airway damage.
The injurious molecule MMP-1 is known to enhance the development of certain devastating lung diseases, such as chronic-obstructive pulmonary disease (COPD), a top-ten ailment in world-wide morbidity and mortality, according to the World Health Organization. The devastating, tissue-destructive actions of MMP-1 can also lead to lung emphysema, which is chronic reduction of the lung surface dedicated to gaseous exchange, and to the spread of lung cancer cells, through migration of these cells from lung tissue that has become cancerous.
The new study also provides a direction for developing therapeutics for those who are genetically more susceptible to air pollution and airway damage, Liedtke said. "If we can find a way to stop the hyperactivation of MMP-1 in response to diesel-engine exhaust particles and reduce it to levels that the airways can manage, then we will be helping a large number of people worldwide," he said. "It is attractive to envision inhaled TRPV4 inhibitor drugs, rather than swallowing a pill or taking an injection. I envision this as rather similar to inhaled drugs for allergic airway disease that are currently available."
Other authors include Jinju Li and Patrick Kanju of the Duke Department of Medicine; Michael Patterson, Wei-Leong Chew, Ryohei Yasuda, and Sidney Simon of the Duke Department of Neurobiology; Tim Oliver of the Duke Department of Cell Biology; Seung-Hyun Cho and Ian Gilmour of the Environmental Protection Agency (EPA) in Research Triangle Park, N.C.; and Andrew Ghio of the EPA in Chapel Hill, N.C. Dr. Yasuda is also a Howard Hughes Medical Investigator.
This research was supported by start-up funds from Duke University and financial support from RJ Reynolds Inc., by a grant of Philip Morris USA Inc. and Philip Morris International, and US-EPA internal funds. Fellowship support came from the Duke University Integrated Toxicology and Environmental Health Program, the Leon-Goldberg Fellowship, and the Research Participation Program in U.S. EPA administered by ORISE.
Mary Jane Gore | EurekAlert!
Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
23.05.2017 | Event News
22.05.2017 | Event News
17.05.2017 | Event News
23.05.2017 | Physics and Astronomy
23.05.2017 | Life Sciences
23.05.2017 | Medical Engineering