Here’s a link to the paper under discussion1: http://www.atsjournals.org/doi/abs/10.1164/rccm.200812-1911OC#.WBcwWvmLR7O
Pollution in our cities is a big problem. Cycling to work every morning through central London exposes me to a broad range of tiny carcinogenic particles. Google maps now labels high pollution areas for the conscientious cyclist to avoid, but sometimes this is impossible, and it is arguable how much distance you actually need to be away from a problem area for this to be effective.
Most face masks designed to protect the wearer from airborne particles have filters that are too large to be effective – most of the harmful stuff is pretty tiny. There is a notable exception in ‘totobobo’ masks, which provide OK protection. Warning – these do not look trendy, and they make it pretty hard to, um, breathe.
The bottom line is that 40 000 people in the UK, and 5.5 to 7 million worldwide die from air pollution every year. More than HIV/AIDS and malaria put together. Let that sink in.
Airborne pollutants have been linked to diabetes recently2, as well as dementia, cancer, obviously, and heart disease3. Different countries produce the unburnt carbon, construction dust and nitrogen dioxide in different ways, and it’s a problem that plagues major conurbations in Africa4 and the UK as much as China and India. Here, there is no sign that we are not stopping – airport expansions, infrastructure for new nuclear power plants, new ports and fracking all release these pollutants.
It’s a public health emergency, that is largely ignored by parliament. The environment is a blind spot for our government, and I definitely don’t think that topic of this paper is a solution. In fact, there is an onus shift going on here: pollutants need not be in the air at all – it should be up to the vast multinationals that make our cars and produce our electricity to end them. In the mean time however, anything that can protect us is worthwhile.
How do the pollutants cause you damage?
The little particles that cause damage can be called xenobiotics – literally foreign particles, and when they get into your lungs they quickly encounter lung-resident cells of your immune system. A little particle of carbon gets into the lungs, and triggers the lung cells to release chemical signals that initiate inflammation: calling the combined forces of the immune system to deal with the threat.
One theory on how the XBs work is that they dry out the lung cells, exposing protruding proteins that can only fold properly in the presence of water. These misfolded proteins might be the ones that send the danger signals.5
Neutrophils, a white blood cell or leukocyte of the immune system, are some of the first responders to the threat. They are highly activated by the misfolding signal from the lung cells. The XBs are both difficult to get rid of, phagocytosis is hard to perform, and more and more of them come in from the environment outside.
What results from the relentless barrage of XBs is a state of chronic inflammation. These powerful immune cells keep coming, due to the signals emanating from the lung cells, and themselves start damaging the lung tissue, which has to repair itself, which gets damaged again, which has to repair itself – all a recipe for disaster as far as your cells are concerned. When cells need to repair themselves like this, there is the potential for mutation in the DNA. Meanwhile the inflammation signals just keep coming and the immune cells, particularly neutrophils, just stay alive and keep fighting.
Unfortunately too much of this and lung cancer, COPD and fibrosis can be the result.
So enter ectoine – it turns out that this compound indirectly returns the level of apoptosis, an important method for control of the immune response, back to normal levels – breaking the cycle of continuous inflammation.
Ancient bacteria can protect us
Ectoine is an amino acid – a chemical we traditionally think of as a building block for proteins – found in archaea or ancient bacteria which must live in a high salt environment. The molecule works by trapping a layer of water around the bacterial cell. For these bacteria, it provides an osmolytic barrier to prevent the cell from losing water and shrivelling up due to the high salt content of the outside environment.
A good layer of water around human cells allows proteins to unfold properly, and therefore to signal. Losing this moisture results in the signals being sent into the cell in response to the mechanical misfolding of these cell membrane proteins, which stick out of the cell like aerials and satellite dishes. A misfolded, furled protein is detected and a damage signal is sent into the cell, which causes them to call the immune system. As discussed above, the neutrophils then exacerbate the immune response to damaging effect over extended periods of time.
Recently, a company called bitop http://www.bitop.de/cms/website.php?id=/en/index/extremolyte/ectoin.htm) latched onto this idea, and commercialised an aerosolised form of ectoine. This aerosolised version is able to be simply applied to the linings of the bronchioles, and was shown in the paper to be effective at reducing the levels of inflammatory cytokines in this area.
This means it may soon be used in an inhaler, as a preventive measure against the damage caused by airborne pollutants in humans.
Written by Michael Shannon
1. Sydlik, U. et al. The Compatible Solute Ectoine Protects against Nanoparticle-induced Neutrophilic Lung Inflammation. Am. J. Respir. Crit. Care Med. 180, 29–35 (2009).
- Wolf, K. et al. Association Between Long-Term Exposure to Air Pollution and Biomarkers Related to Insulin Resistance, Subclinical Inflammation and Adipokines. Diabetes (2016). doi:10.2337/db15-1567
- Wilker, E. H. et al. Long-Term Exposure to Fine Particulate Matter, Residential Proximity to Major Roads and Measures of Brain Structure. Stroke (2015).
- Roy, R. The cost of air pollution in Africa. (OECD Publishing, 2016). doi:10.1787/5JLQZQ77X6F8-EN
- Sydlik, U. et al. Recovery of neutrophil apoptosis by ectoine: a new strategy against lung inflammation. Eur. Respir. J. 41, (2013).