{"id":1904,"date":"2015-11-01T13:49:21","date_gmt":"2015-11-01T12:49:21","guid":{"rendered":"http:\/\/www.samuelfurse.com\/?p=1904"},"modified":"2015-11-01T15:07:11","modified_gmt":"2015-11-01T14:07:11","slug":"two-is-company-three-is-lung-damage","status":"publish","type":"post","link":"http:\/\/www.samuelfurse.com\/2015\/11\/two-is-company-three-is-lung-damage\/","title":{"rendered":"Two is company, Three is Lung Damage"},"content":{"rendered":"

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Diseases related to chronic lung damage kill about 25,000 people a year in Great Britain. That is about 40 per 100k of population. \u00a0What this figure does not say is what it is like to live with the diseases, what might make them worse or cause it to start with, or what the underlying molecular changes are. Much of the damage involved in these conditions is due to long term exposures such as smoking and mineral dust.<\/p>\n

Needless to say, physicians have ready advice for those suffering from the conditions. \u00a0This advice has arisen from observations about the results of exposure to hot and cold weather, and pollution. Experience has also suggested that a particular geranium-scented gas is also a problem for sufferers of chronic lung conditions and can also damage healthy lungs, and thus by extension a low-level problem for the rest of us. It is heavily ironic that this gas should be dangerous, as the atoms that make it up are essential for life on Earth as we know it.<\/p>\n

The gas is ozone. It is a molecule made of three atoms of oxygen. \u00a0Oxygen molecules, that are essential to our continued existence, comprise just two atoms. Recently, it has begun to become clear exactly why this gas is so dangerous to lungs at a molecular level. Research carried out at Birkbeck College, University of London, using surface tension measurements has demonstrated that ozone interacts with a number of the molecular species resident in the lungs that are essential for its proper function. These include the molecular species that make up the bulk of the lipid fraction of lung surfactant [1, 2, 3]. Most recently, this research programme has produced evidence that the protein fraction of lung surfactant is also susceptible to low levels of ozone [4], also using surface tension measurements.<\/p>\n

Surface tension is a measure of the physical properties of a lipid membrane or monolayer, and is useful because it affects the key role of the lungs, absorbing oxygen.<\/p>\n

The protein studied is called Lung Surfactant Protein B (SP-B). It is made in the lungs and is located at the interface between the air and the fluid part of the lung. Like the lipids when they are exposed to ozone, there is a chemical reaction that causes an effective permanent change to the molecules affected. However, the effect of the ozone on lipids and the proteins is a bit different.<\/p>\n

When the lipids are exposed to ozone, the surface tension of the surface the lipids form, goes down rather rapidly, before increasing to a point above where it normally is or should be for efficient lung function. However, this does not correlate with the effects observed after ozone exposure to humans [5]. The toxic effects of ozone are observed much later, quite unlike the effects of many toxic gasses such as cyanide or phosgene, that are essentially immediate. This raised the question of what else might be happening. It was certain that ozone was doing damaging things to the lipids, and that the lipids were essential for lung function, but the reason for the delay was not clear.<\/p>\n

Interest therefore fell upon other components of the surfactant, to see what happened when they were exposed to ozone. Interestingly, the effect of ozone damage to SP-B causes an immediate increase in surface tension [5]. This is in the opposite direction to the decrease caused by the effect on lipids [2]. This delay does not last that long\u2014perhaps half an hour in the experimental model systems\u2014but is long enough to confound superficial observation of the effects of ozone on a mammal’s lungs.<\/p>\n

The molecular approach to solving this problem not only answered an important question about lung function on exposure to ozone, it did so in a manner that could not have been achieved really any other way. Ideas about the relationship between surface tension, lung function and oxygenation had been established [6], but a physical molecular approach was required to get to the molecular heart of the problem. It represents a modern application of a scientific approach called reductionism: to break down a system into its component parts, and understand that system in terms of the behaviour of the individual parts and their relationships with each other.<\/p>\n

Quite what the molecular relationship between ozonolised lipids and SP-B is in vivo<\/em> is not at present clear, and thus may form part of a research question that has yet to be tackled.<\/p>\n

References<\/strong><\/p>\n

[1] K. C. Thompson, A. R. Rennie, M. D. King, S. J. O. Hardman, C. O. M. Lucas, C. Pfrang, B. R. Hughes, A. V. Hughes
\nLangmuir<\/em>, 2010<\/strong>, 6<\/em>, 17295\u201317303. DOI: 10.1021\/la1022714.<\/p>\n

[2] K. C. Thompson, S. H. Jones, A. R. Rennie, M. D. King, A. D. Ward, B. R. Hughes, C. O. M. Lucas, R. A. Campbell, A. V. Hughes, Langmuir<\/em>, 2013<\/strong>, 29<\/em>, 4594\u22124602. DOI: 10.1021\/la304312y.<\/p>\n

[3] L. Q.ao, A. Ge, Y. Liang, S. Ye, J. Phys. Chem. B<\/em>, 2015<\/strong>, Just Accepted Manuscript. DOI: 10.1021\/acs.jpcb.5b08985.<\/p>\n

[4] J. M. Hemming, B. R. Hughes, A. R. Rennie, S. Tomas, R. A. Campbell, A. V. Hughes, T. Arnold, S. W. Botchway, K. C. Thompson, Biochemistry<\/em>, 2015<\/strong>, 54<\/em>, 5185\u22125197. DOI: 10.1021\/acs.biochem.5b00308.<\/p>\n

[5] R. B. Devlin, K. E. Duncan, M. Jardim, M. T. Schmitt, A. G. Rappold, D. Diaz-Sanchez, Circulation<\/em>, 2012<\/strong>. DOI: 10.1161\/circulationaha.112.094359.<\/p>\n

[6] M. Ikegami, T. E. Weaver, S. N. Grant, J. A. Whitsett, Am. J. Respir. Cell. Mol. Biol.<\/em>, 2009<\/strong>, 41<\/em>, 433\u2013439. DOI: 10.1165\/rcmb.2008-0359OC.<\/p>\n

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