Pollen alters the immunological rather than the physical barrier of the pulmonary mucosa
The mucous membrane of the lungs forms a barrier to harmful substances which we breathe in. This barrier is made up of different elements. Firstly the cells of the mucosa form a mechanical barrier. They are joined together by anchoring molecules. A chemical barrier is maintained by substances that are released onto the surface of the cells. The immunological barrier denotes a number of messen- gers which are produced by the mucosal cells but exert their action not on the surface but on cells of the immune system lying below the skin.
Inflammatory reactions are mediated and regulated by this immunological barrier. In a cooperative project of Research Area A with the University of Southampton, UK, we were able to discover that grass pollen leaves the mechanical barrier of pulmonary mucosal cells unaffected but does alter the immunological barrier. This research was performed on an in vitro skin model with primary, human epithelial cells. Histological investigations showed that the anchoring molecules, known as the «tight junctions» of the mucosal cells, are not altered when the artificial mucosa comes into contact with pollen. However, messengers released by the epithelial cells were greatly altered by pollen contact. The transporting of messengers outwards as well as inwards was changed by pollen. This is a clear signal that pollen itself can make changes at the mucosa and can initiate inflammatory processes. This finding is alarming particularly because the effects happen independently of the allergen, which means they can definitely occur in non-allergic individuals as well. Hence this result adds another aspect to the big picture of what effects pollen has on human individuals.
Environment, Allergens and Exposure Toxicity of airborne particles from elementary school indoor air
A Munich research consortium of TUM, LMU and Bavarian Ministery for Health, called PAMINA (PArticle Monitoring in ambient and INdoor Air) investigated with the help of CK-CARE the air quality in Bavarian schools. From previous investigations it was known that school indoor air contains high levels of coarse and fine dust, scientifically called Particulate Matter with a diameter <10µm (PM10). In schools, average levels of PM10 were about 120µg/m3, with values up to 450µg/m3, whereas by law outdoor concentrations are not allowed to exceed 50µg/m3. The consortium tried to answer the question if indoor school PM10 was less toxic than outdoor PM10.
Prof. Buters, Dr. Öder and colleagues took airborne indoor samples for one month in each classroom at several schools during teaching hours. Not an easy undertaking as the instruments, although noise reduced, still disturbed the children and the teachers.
The indoor particles were different form outdoor particles as they contained more silicates (sand) and organic material (probably human skin). Classic toxicology showed limited toxicity of the indoor particles. However, with genome wide screening of human immortalized lung cells after exposure to indoor and outdoor particles, a clear differences were noticed. Indoor air, already on an equal weight basis, was more active in changing SERPIN B2, a gene involved in blood coagulation, activated more inflammatory markers (CCl20, CXCL6, IL-6 etc.), and was more active in changing xenobiotica metabolizing enzymes (CYP1A1, CYP1B1) than outdoor air. The findings on a genetic basis were confirmed with other methods: indoor PM10 enhanced human blood coagulation, the inflammatory markers correlated with LPS (lipopolysaccharides, a marker for bacteria), and certain indoor (but also outdoor) organic compounds correlated only with the xenobiotica metabolizing enzymes. Surprisingly, school indoor air also contained the allergens of cat, dog and mice but not house dust mite, the number one airborne allergen in Europe, or cockroach. The levels were high enough to activate human basophils of cat allergic individuals.
With the used systems four effects were thus detected in school indoor air particles: blood coagulation, inflammation, changed xenobiotica metabolism, and allergic activation. All these effects were absent when using the same amount of outdoor PM10 sampled in front of the schools. If we then consider that indoor PM10 is 6-fold higher than outdoor PM10, on an equal inhaled air volume the situation would be even more pronounced.
Our findings need confirmation if the observed effects actually occur in school children. Until then, venting classrooms with outdoor air seems a sensible option.
Dr. Sebastian Öder and Prof. Dr. Jeroen Buters
CPD Congress in Davos
For the 29th time the congress “Advances in allergology, dermatology, pneumology and immunology“ took place in Davos. It was held from11 to 14 September 2013 and was organised by the Skin and Allergy Clinic Biederstein of the Technical University of Munich in conjunction with CK-CARE.
In 18 plenary lectures internationally recognised experts explaines important developments from broadly diverse areas of allergy medicine – from hay fever, asthma, allergic skin diseases, food allergies through to inflammatory diseases and problems of mental wellbeing associated with allergies.
The congress started every morning with case presentations of selected clinical pictures followed by discussion. In the afternoon over 220 participants divided into smaller groups for interactive seminars and workshops with practical exercises. The key themes included the treatment of severe “Asthma“, “Allergen-specific immunotherapy“, “Skin on fire“, “New therapies“ as well as “Paediatric dermatology“ and “Itching“. A specific seminar addressed “Emergency medicine“, where the current therapeutic measures in life-threatening anaphylaxis could be presented and practised. “Acupuncture“ in allergic diseases and “Nutrition therapy“ were also on offer.
The keynote speech was given by Professor Tilo Biedermann from Tübingen on the subject “Contact and consequences – how it gets under our skin!“
Another highlight was the celebration of 20 years of the Kanert Foundation with the award of the Kanert Prize for Allergy Research, which went to Professor Stephan Weidinger from Kiel for a project on epigenetic studies in monozygotic twins with atopic eczema.
In his opening address Professor Johannes Ring from Munich referred to the difficulties that will be faced by many patients and staff due to closure of the Hochgebirgsklinik for economic reasons. In past decades, the Hochgebirgsklinik has provided thousands of patients with relief, improvement of their chronic illness or a cure.
Team meeting 2013
In the run-up to the 29th CPD Congress “Advances in allergology, dermatology, pneumology and immunology“, directors and staff of all CK-CARE research areas came together for their annual team meeting. In addition, participants in the exchange programmes and those responsible for the cooperative projects (including PD Dr. Stéphanie Christen-Zäch, Lausanne, and Mr. Pingel Keuth, Aachen) were invited to the scientific exchange.
All research departments gave progress reports, by means of posters and presentation, on the work being undertaken.
This provided a deep insight into the projects and initiated a lively exchange among the departments. Several possible areas of cooperation were identified and are now being translated into action items. The objective of the team meeting – to create added value through collaboration between the research areas – was thus achieved.
What happens in the skin and the blood during atopic eczema?
In order to strengthen the existing close cooperation between research areas of CK-CARE, a stand-alone “central project“ was first launched in summer 2013, in which all research departments are involved to varying degrees. Out of various applications, the scientific advisers of the board of directors selected the project “Microbiome of the skin and transcriptome analysis of lymphocytes for investigation of different subpopulations of patients with atopic eczema (neurodermatitis)“. The project is is jointly led by the scientific directors Prof. Dr. Johannes Ring, Prof. Dr. Cezmi Akdis, Prof. Dr. Roger Lauener, Prof. Dr. Claudia Traidl-Hoffmann.
Among the different manifestations, the extrinsic form of neurodermatitis (in which there is evidence of IgE antibodies and specific sensitisation) will be assessed versus the “intrinsic“ variant, which shows a similar clinical picture without proof of IgE involvement.
The analyses will be complemented by comparisons with healthy control subjects. The clinical examinations will be performed mainly in adults at the Department of Dermatology and Allergy Biederstein of Munich Technical University (Prof. Johannes Ring, PD Dr. Kilian Eyerich) and the Department of Dermatology and Allergy of Hochgebirgsklinik Davos (Dr. med. Matthias Möhrenschlager). The cell cultures for analysing the transcriptome are produced collaboratively by ZAUM(Centre for Allergy and Environment of the Technical University of Munich – Prof. Claudia Traidl-Hoffmann) and the Swiss Institute of Allergy and Asthma Research SIAF (Prof. Cezmi Akdis).
The microbiome analyses of the cutaneous microflora are being performed in ZAUM in collaboration with the Science Centre Weihenstephan of the Technical University of Munich. As well as blood samples, tissue specimens from affected and unaffected skin areas will also be collected. These studies will only be performed in adults. Involvement of the Children’s Clinic of St. Gallen Cantonal
Hospital (Prof. Roger Lauener) is in preparation. The studies may be expected to yield highly interesting results for better characterisation of different forms of neurodermatitis, from which it might be possible to derive new practical approaches to diagnostics and treatment.
The influence of ozone on Ambrosia artemisiifolia pollen
Ambrosia artemisiifolia (common ragweed), an invasive neophyte From North America, is spreading increasingly in Europe. This annual plant produces up to a billion pollen grains with very high allergenic potential. Research in recent years has shown that climate change and environmental pollution have an influence on the growth and the flowering period of plants.
Tropospheric ozone is among the environmental gases relevant to climate that poses a direct risk to human health. In a cooperative project with the Helmholzzentrum Munich, it was analysed in a controlled climate chamber experiment whether ozone can also induce stress in the plant and whether that in turn influences the expression of allergens. Ambrosia plants were gassed with defined concentrations of ozone (40 ppb ozone = control (ambient); 80 ppb ozone = increased) and their pollens were compared with each other. It was found that an increase in ozone to twice the ambient concentration led to a change in the pollen cell wall (less wax and more pectin). Transcriptome analysis by 454 sequencing reflected these results. An increase in so-called stress genes (e.g. monodehydroascorbate reductase) was also demonstrated in response to increased ozone. There was also an ozone-dependent, isoform-specific increase in Ambrosia allergen transcripts
Furthermore homologues to other different plant allergens, e.g. Sal k 1 (pectin methylesterase) and Sal k 2 (protein kinase), were foundwhich had increased transcript quantities under the influence of ozone. Such homologues might also have an allergenic influence in Ambrosia because these proteins might represent hitherto unknown Ambrosia allergens. At the protein level (ELISA analyses), however, the main allergen Amb a 1 showed no significant difference between ozone-treated and control pollen. Nevertheless, an altered allergenic potential cannot be ruled out because an increased potential has already been demonstrated in various plant species even without an increased quantity of allergen being present. At the same time the allergenicity of pollen is not solely dependent on the allergen. In fact small-molecular, nonallergenic substances also play a role. Whether ozone has an influence on these substances is currently being analysed in another CK-CARE project.
Climate change and prosperity - Poor outlook for allergy sufferers
At the Global Allergy Forum in Davos, Allergy researchers from all over the world, who met from 16 to 19 June, warn that climate change with all its facets will have a particular impact on allergy sufferes.
The unanimous opinion of the 40 top researchers is that, according to the current state of research the «allergy» epidemic will continue to grow. The scientists cited among others the following reasons for this statement, namely, with the increase in temperature new allergy-inducing plants such as Ambrosia appear and the flowering periods of trees, and with that the pollen season, is being prolonged. Symptoms are amplified and extended in their seasonal occurrence. Forecast – hayfever throughout the year! In addition, particularly economically highly developed cultures will suffer under the epidemic allergy. Environmental pollution, diet, and increased standards of hygiene are named as the main reasons. A huge concern is the development of allergic diseases in developing countries for which the allergy researchers predict a more rapid increase in allergies as compared to the development in Europe.