Key words :
climate change,
lung
,air pollution
,climcate change
,immune system
,ozoné
,endotoxin
,health
,immunology
Ozone Modifies Pulmonary Innate Immune Response
18 Oct, 2007 09:56 am
It is well known that air pollution can cause health problems in susceptible populations. Our study, recently published in the Journal of Immunology, focused on how exposure to ozone predisposes to a worsening of lung problems.
Air pollution is caused by incomplete combustion of fossil fuels like coal and gasoline by industry or by vehicle engines. This incomplete combustion produces air-borne particulate matter, tiny dust-like particles that can be inhaled, but also several types of gases that are released in the atmosphere, like nitrogen dioxide. Nitrogen dioxide reacts with the oxygen in the atmosphere, and produces ozone, a highly reactive molecule with 3 oxygen atoms. This reaction requires energy in order to happen, and this energy is provided by sunlight. Therefore, polluting ozone is particularly produced during sunny days in areas with cars or industry. Most people recognize ozone from the protective layer in the upper atmosphere, which blocks the sun’s UV rays. However, ozone in the lower atmosphere can be toxic, because it is highly reactive and can injure cells and tissues when inhaled.
Several scientists have discovered that ozone exposure can lead to health problems, particularly in people with heart and lung disease. Among others, David Peden from the University of North Carolina has pointed out that ozone worsens allergic symptoms of asthmatics. Other investigators have identified that, in the few days after ozone exposure, emergency room visits and hospital admissions for asthma, bronchitis and pneumonia are increased. These findings indicated that ozone may alter the immune system in a way that makes it more vulnerable to additional attacks from bacteria or other pollutants. Numerous studies support direct toxic effects of ozone on many cell-types in the lung. Steve Kleeberger from the USA National Institutes of Health initially identified that genes of innate immunity can contribute to the biologic response after ozone exposure. Innate immunity is a specific part of the immune system, which immediately recognizes and fights microorganisms and toxic agents without prior prompting or programming. However, the effects of ozone on subsequent innate immune responses had not been fully appreciated.
Our study, recently published in the Journal of Immunology , focused on how exposure to ozone predisposes to a worsening of lung problems. We hypothesized that prior exposure to ozone would change the innate immune response of the lungs to a subsequent endotoxin exposure. Endotoxin is the active portion of gram-negative bacteria, and can commonly be found in household dust or air pollution in the urban environment, particularly in inner cities. Therefore, inhaled endotoxin is a reasonable experimental substitute for lung infection or toxic exposures. Additionally, bacterial endotoxin is specifically recognized by the innate immune system.
In our experiments, we had mice breathe filtered air or air containing ozone, to model what an exercising human would breathe in on a high-ozone-alert day. One day later, we exposed mice to inhaled endotoxin. Our experiments showed two important findings.
First, we found that after ozone exposure, the lung becomes much more injured when exposed to endotoxin, compared to just endotoxin exposure. Additionally, mice showed a much higher tendency to have asthma-like airway reactions with the ozone-endotoxin exposure, as opposed to either ozone or endotoxin alone. We found that this was the result of mobilization of a specific innate immune receptor to the surface of inflammatory cells, which therefore was much more likely to bind endotoxin and enhance response to this toxin exposure.
Our second, surprising finding was that there were fewer macrophages in the lungs of animals pre-exposed to ozone. We recognized that these immune cells started dying off after ozone exposure, not only in the lung, but also in the blood. That happened because ozone triggered reactions in these cells that caused them to commit programmed cell death (also known as apoptosis). As a result of ozone exposure, fewer macrophages were available in the airspace. Fewer macrophages suggest the host would have an impaired innate ability to fight inhaled bacterial pathogens, which could contribute respiratory infections.
Thus, our study highlights the importance of co-exposures to inhaled environmental toxicants and may help explain some key effects of human ozone exposures. People are more likely to suffer asthma and bronchitis exacerbations after breathing ozone. Ozone primes the innate immune response in the lung to bacterial endotoxin resulting in enhanced lung injury, increased airway responsiveness, and reduced numbers of viable macrophages. This might, in part, explain why admissions for infectious bronchitis and pneumonia are more common after high-ozone days.
The results of our study may help scientists and environmental agencies determine how ozone affects human health, and what the possible risks are after ozone exposure. Many government regulatory bodies are currently evaluating the standards for allowable levels of ozone in the air, and some are pushing for lower permissible levels, because of possible adverse health effects.
Reference
John W. Hollingsworth, et al. (2007) Ambient Ozone Primes Pulmonary Innate Immunity in Mice. Journal of Immunology 2007; 179: 4367-4375.
Key words :
