A pathway regulating neutrophil integrin inactivation and its contribution to inflammation

Lead Research Organisation: University of Edinburgh
Department Name: MRC Centre for Inflammation Research

Abstract

The body's immune cells generate inflammation as part of their defence against infections. But sometimes, immune cells generate inflammation even in the absence of infection. Chronic inflammatory conditions, such as rheumatoid arthritis or multiple sclerosis cause much suffering and pose a massive drain on health services world-wide. To generate inflammation, a type of white blood cell called the neutrophil is essential. Neutrophils are the most common type of white blood cell. Neutrophils are recruited from the blood stream to sites of infection or injury. In order to leave the bloodstream, neutrophils become sticky: they adhere to the inside of the wall of the blood vessel before they transmigrate. This process relies on particular cell surface molecules, the integrins. Integrins exist in a "sticky" (active) and a "non-sticky" (inactive) conformation. It's already known that absence of integrins, or their inability to become activated interferes with the recruitment of neutrophils to sites of infection. A small number of studies analysed integrins that were experimentally rendered permanently active. These activated integrins, too, did not support neutrophil recruitment. We recently showed that a cellular regulator called ARAP3 is important for the regulation of neutrophil integrins, allowing activated integrins to become inactive. Loss of ARAP3 changes the activity profile of the neutrophil. For example, it interferes with migration in the test tube, as neutrophils adhere too firmly to the underlying support. We think that neutrophils need to be able to activate, and inactivate their integrins, "fine-tuning" integrin activity for optimal migration through the body's tissues. Therefore, loss of ARAP3 may also interfere with neutrophil recruitment, and ultimately inflammation. We will study this in the test tube and in models for neutrophil recruitment and for inflammation. We think that ARAP3 is a good target for combating inflammation. This work will build the foundations for new therapeutic approaches targeting chronic inflammation.

Technical Summary

The proposed work explores modulation of the activity status of neutrophil integrins, specifically integrin inactivation, and how this critically regulates neutrophil transendothelial migration, neutrophil recruitment and inflammation. The work builds onto our recent in vitro work, that demonstrated that the GTPase activating protein (GAP) ARAP3 is a negative regulator of beta2 integrin activity and integrin-dependent processes in the neutrophil. The proposed work will analyse primary murine and human neutrophils, as well as (human) PLB-985 cells, which are amenable to lentiviral transduction and can be induced to behave neutrophil-like. Three aims will be addressed. (1) To characterise which neutrophil integrins are regulated by ARAP3 in terms of their activity status, the mechanism by which this occurs (surface availability and/or activity status), and whether this activity is conserved between murine and human neutrophils. (2) To identify how this modulation of integrins affects neutrophil transendothelial migration in vitro, and neutrophil recruitment to sites of sterile inflammation in vivo. (3) To address the effects of ARAP3-dependent regulation of neutrophil integrins on the induction, persistence and resolution of inflammation in models of acute and chronic inflammation. The proposed work will contribute to our understanding of the regulation of neutrophil integrins, analysing their inactivation, a previously underexplored step. This work will furthermore characterise the importance of integrin inactivation to neutrophil recruitment and inflammation. The work may lay the foundations to the development of new therapeutic approaches targeting neutrophil integrin inactivation in chronic inflammation.

Planned Impact

The proposed work will generate impact at a number of levels.

This is fundamental research aimed to understand the molecular control of neutrophils, which are involved in the generation of chronic inflammation. The primary immediate beneficiaries will be the wider academic biomedical science community in the UK and abroad. Visibility will be achieved by publishing our work in peer-reviewed journals with a broad readership. In agreement with MRC policies, our work will be published as open access articles, broadening the readership further still.

The main impact of the proposed research lies in the generation of new knowledge and scientific advancements, an established strength of the UK economy. Tackling a mechanism that underpins chronic inflammation, our scientific research will provide the basis for future translational research. The work will be of immediate benefit for the wider academic community, of indirect benefit for the pharmaceutical sector, and ultimately benefit patients.

The private sector will benefit from the proposed work. We are already exploring shared interests in neutrophil biology and inflammation with colleagues at Blueberry Therapeutics. This resulted in the recent submission of a joint CASE studentship application to MRC.

The general public will also benefit from the proposed work, thanks to public engagement activities aimed at both adults and children. We target local schools and present at the Edinburgh International Science Festival, which is held annually and draws in a very large audience.

Publications

10 25 50
 
Description Industrial CASE CVS
Amount £98,212 (GBP)
Funding ID BB/R505651/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2017 
End 09/2021
 
Description MRC Precision Medicine PhD Doctoral Training Programme studentship
Amount £88,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2019 
End 08/2023
 
Description MRC project grant (HoxB8 neutrophils)
Amount £408,851 (GBP)
Funding ID MR/S008020/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2019 
End 04/2022
 
Description PhD Scholarship
Amount £107,953 (GBP)
Funding ID 21577 
Organisation Versus Arthritis 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2017 
End 09/2020
 
Description Project Grant
Amount £237,663 (GBP)
Funding ID PG/17/54/32981 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2017 
End 09/2020
 
Title HoxB8 neutrophils 
Description We showed that conditionally immortalised HoxB8 haematopoietic progenitor cells, unlike neutrophil-like cell lines, faithfully replicate signalling and effector functions observed with primary mouse neutrophils. This includes integrin and Fcgamma receptor induced functions, for which neutrophil-like cell lines are very poor models. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2019 
Provided To Others? Yes  
Impact The use of HoxB8 neutrophils has the potential to very significantly reduce mouse use, since it will avoid preparation of fresh neutrophils from a mouse for each individual experiment. 
 
Description ARAP3 in osteoclasts (Paget's Disease of Bone patient cohort) Laetitia Michou, Universite Laval 
Organisation University Hospital of Laval University
Country Canada 
Sector Hospitals 
PI Contribution Help with experimental design and donation of research reagents.
Collaborator Contribution Identified novel SNP in a disease cohort
Impact Named collaborator on a grant proposal (Canadian funding agency)
Start Year 2017
 
Description Collaboration with GSK (Gus Amour) 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution intellectual input
Collaborator Contribution access to expertise
Impact we wrote a research proposal together and won a BBSRC CASE studentship (2017-21)
Start Year 2016
 
Description Collaboration with Inge Hers, Bristol 
Organisation University of Bristol
Department Bristol Centre for Surgical Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual input
Collaborator Contribution training of staff
Impact access to new methods to approach our research questions DOI: 10.4049/jimmunol.1900443
Start Year 2018
 
Description Collaboration with Johanna Ivaska Lab, Turku University, Finland 
Organisation University of Turku
Department Turku Centre for Biotechnology
Country Finland 
Sector Academic/University 
PI Contribution intellectual contribution
Collaborator Contribution intellectual contribution, access to research protocols and contribution in kind of a reagent (recombinant protein)
Impact This collaboration has helped our project forward a great deal and resulted in a shared publication. DOI: 10.4049/jimmunol.1900443
Start Year 2017
 
Description Collaboration with Leo Carlin, Beatson Institute 
Organisation Beatson Institute for Cancer Research
Country United Kingdom 
Sector Academic/University 
PI Contribution expertise and intellectual input
Collaborator Contribution access to equipment
Impact this allowed us to use a technique that would otherwise have been outside of our reach; the results were included in a publication DOI: 10.4049/jimmunol.1900443
Start Year 2016
 
Description Collaboration with Robert Insall, Beatson Institute 
Organisation Beatson Institute for Cancer Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Exchange of expertise and enabling visits and of our equipment by a member of the collaborating laboratory
Collaborator Contribution Exchange of expertise
Impact We wrote a research proposal together, and won a MRC Precision Medicine Studentship (2019-23).
Start Year 2017
 
Description Takehiko Sasaki 
Organisation Tokyo Medical and Dental University
Country Japan 
Sector Academic/University 
PI Contribution experiments, data analysis
Collaborator Contribution provided valuable reagents
Impact DOI: 10.4049/jimmunol.1900443
Start Year 2012
 
Description 1. 13th London World Congress on Inflammation, July 8-12, 2017. Hilton London Metropole Hotel, London. GREMI (Groupe de Recherche et Etude des Médiateurs de l'Inflammation) Symposium. "Roscovitine as a new anti-inflammatory therapy promoting neutrophil apoptosis". 9th July 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 13th London World Congress on Inflammation, July 8-12, 2017. Hilton London Metropole Hotel, London. GREMI (Groupe de Recherche et Etude des Médiateurs de l'Inflammation) Symposium. "Roscovitine as a new anti-inflammatory therapy promoting neutrophil apoptosis". 9th July 2017.
Year(s) Of Engagement Activity 2017
URL http://wci2017.org
 
Description 1. Pharmacology 2017, 11-13 December 2017, Queen Elizabeth II Conference Centre, London. The Japanese Pharmacological Society (JPS) and the British Pharmacological Society (BPS) Symposium. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 11th December 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Pharmacology 2017, 11-13 December 2017, Queen Elizabeth II Conference Centre, London. The Japanese Pharmacological Society (JPS) and the British Pharmacological Society (BPS) Symposium. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 11th December 2017.
Year(s) Of Engagement Activity 2017
URL https://www.bps.ac.uk
 
Description 1. Society for Reproductive Investigation (SRI); Scientific Symposium Targeting Inflammation to Improve Reproductive Health Across the Lifecourse (John McIntyre Conference Centre, Edinburgh, 16-18th August 2017). "Enhancing the resolution of inflammation as a potential therapeutic target in the reproductive system" 17th August 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Society for Reproductive Investigation (SRI); Scientific Symposium Targeting Inflammation to Improve Reproductive Health Across the Lifecourse (John McIntyre Conference Centre, Edinburgh, 16-18th August 2017). "Enhancing the resolution of inflammation as a potential therapeutic target in the reproductive system" 17th August 2017
Year(s) Of Engagement Activity 2017
URL https://www.ed.ac.uk/files/atoms/files/sri_programme_updated_14.8.2017.pdf
 
Description 3R conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact This presentation showcased a refinement for tamoxifen-dependent Cre induction in inducible knock-out mice.
Year(s) Of Engagement Activity 2016
 
Description 7th Munster Immunology meeting Keynote speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 7th Munster Immunology meeting. Theme: Growing diversity in the Immune System. Keynote speaker talk entitled "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration" 29th November 2019.
Year(s) Of Engagement Activity 2019
 
Description An invited talk in Quebec, Canada 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The presentation was followed by a Q&A session and has resulted in a series of follow-up conversations and new collaborations
Year(s) Of Engagement Activity 2017
 
Description BSI conference 2019 (Utsa) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Member of the organising panel for the BSI 'Inflammation' Early Careers Day and chair of the 'Careers Panel' that was held in Edinburgh on 24/4/2019 as part of the British Society for Immunology Conference 'Inflammation - From Initiation to Restoration'
Year(s) Of Engagement Activity 2019
URL https://www.immunology.org/events/inflammation-initiation-restoration
 
Description Banff, Canada 2017. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 10th Biennial Banff Inflammation Workshop (26-29th January 2017). Talk on 27th January 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Banff, Canada 2017. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 10th Biennial Banff Inflammation Workshop (26-29th January 2017). Talk on 27th January 2017.
Year(s) Of Engagement Activity 2017
URL https://www.ucalgary.ca/biw2017/
 
Description British Association Lung Research (BALR) Summer Meeting. Discovery to Recovery: still lost in translation? Queens University, Belfast. 30th August-1st September 2017. Zebrafish and mouse models of 'lung' inflammation - pros and cons! 31st August 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact British Association Lung Research (BALR) Summer Meeting. Discovery to Recovery: still lost in translation? Queens University, Belfast. 30th August-1st September 2017. Zebrafish and mouse models of 'lung' inflammation - pros and cons! 31st August 2017
Year(s) Of Engagement Activity 2017
URL https://www.balr.co.uk
 
Description Cardiff University, Cardiff School of Dentistry. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 3rd March 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Cardiff University, Cardiff School of Dentistry. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 3rd March 2017.
Year(s) Of Engagement Activity 2017
 
Description Edinburgh International Festival 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Workshop on 'Amazing Immunology' that took part over four consecutive days as part of the Edinburgh Science Festival. This particular event was aimed at children aged 7-12, with 20 children taking part on each of four days. The Edinburgh Science Festival is one of Europe's largest Science festivals. It is held annually in the Easter school vacations, drawing tens of thousands of visitors from Edinburgh, The Lothians, Scotland and beyond.
Year(s) Of Engagement Activity 2019
URL http://www.sciencefestival.co.uk/festival
 
Description Edinburgh International Science Festival 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Participation in a workshop on immunology aimed at children (20 children / session; ie 80 children in total, aged 8-12 years) that ran for 1 hr a day throughout the Edinburgh International Science Festival that took place in during the Easter school holidays 2018.
Year(s) Of Engagement Activity 2018
URL https://www.sciencefestival.co.uk/festival
 
Description FASEB SRC on Small GTPases Florida 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Participation in this conference involved a number of interesting talks, and helpful Q&A sessions. This resulted in a new collaboration (reported separately)
Year(s) Of Engagement Activity 2017
 
Description Invited speaker at Summer School, Leiden, Netherlands 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Summer School, Leiden, Netherlands. 8-12 July 2019. Immune modulation in human and animal infection; impact on health, disease and therapy. Lecture on the 10th July 2019 entitled "Host-directed therapies and check point modulation in infectious disease".
Year(s) Of Engagement Activity 2019
 
Description MRC Centre for Inflammation away day, Appleton Tower, Edinburgh. "Therapeutic Strategies to Enhance the Resolution of Inflammation to Promote Tissue Repair and Regeneration". 29th June 2017 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact MRC Centre for Inflammation away day, Appleton Tower, Edinburgh. "Therapeutic Strategies to Enhance the Resolution of Inflammation to Promote Tissue Repair and Regeneration". 29th June 2017
Year(s) Of Engagement Activity 2017
URL https://www.ed.ac.uk/inflammation-research
 
Description Our papers are frequently highlighted in the press 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A list of manuscript published by my research team and collaborators that have been highlighted in the University websites and twitter accounts and the general press are listed below (some examples of media outlets have been given).

Dorward DA, Felton JM, Robb CT, Craven T, Kipari T, Walsh TS, Haslett C, Kefala K, Rossi AG, Lucas CD. The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome. Thorax. 2017 Feb;72(2):182-185. doi: 10.1136/thoraxjnl-2016-209229. PubMed PMID: 27965411; PubMed Central PMCID: PMC5284332.

http://science.newsln.jp/news/2016110315440074.html
https://scifeeds.com/news/immune-cell-insight-offers-hope-for-tackling-deadly-lung-condition/

Hoodless LJ, Lucas CD, Duffin R, Denvir MA, Haslett C, Tucker CS, Rossi AG. Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo. Sci Rep. 2016 Nov 11;5:36980. dei: 10.1038/srep36980. PubMed PMID: 27833165; PubMed Central PMCID: PMC5105078.

http://www.eveningtimes.co.uk/news/14987467.Zebrafish_used_by_Scots_scientists_to_help_study_new_therapies_for_lung_disorders/
http://www.heraldscotland.com/news/14987467.Zebrafish_used_by_Scots_scientists_to_help_study_new_therapies_for_lung_disorders/
http://scientists.trendolizer.com/2017/01/zebrafish-used-by-scots-scientists-to-help-study-new-therapies-for-lung-disorders.html


Brook M, Tomlinson GH, Miles K, Smith RW, Rossi AG, Hiemstra PS, van 't Wout EF, Dean JL, Gray NK, Lu W, Gray M. Neutrophil-derived alpha defensives control inflammation by inhibiting macrophage mRNA translation. Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4350-5. dei: 10.1073/pnas.1601831113. PubMed PMID: 27044108; PubMed Central PMCID: PMC4843457.

http://immunitytales.com/a-molecular-brake-for-macrophage-driven-inflammation/
https://scifeeds.com/journal-article/neutrophil-derived-alpha-defensins-control-inflammation-by-inhibiting-macrophage-mrna-translation/
https://www.sciencedaily.com/releases/2016/04/160418120337.htm
http://www.ed.ac.uk/news/2016/arthritis-treatment-hope
http://www.dailymail.co.uk/health/article-3546735/Treatments-halt-pain-arthritis-set-developed-discovery-body-s-defence-switched-against-condition.html

Duffin R, O'Connor RA, Crittenden S, Forster T, Yu C, Zheng X, Smyth D, Robb CT, Rossi F, Skouras C, Tang S, Richards J, Pellicoro A, Weller RB, Breyer RM, Mole DJ, Iredale JP, Anderton SM, Narumiya S, Maizels RM, Ghazal P, Howie SE, Rossi AG, Yao C. Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis. Science. 2016 Mar 18;351(6279):1333-8. dos: 10.1126/science.aad9903. PubMed PMID: 26989254; PubMed Central PMCID: PMC4841390

https://www.eurekalert.org/pub_releases/2016-03/uoe-iss031616.php
https://www.sciencedaily.com/releases/2016/03/160317150759.htm
http://www.sciencecodex.com/immune_study_shows_how_gut_keeps_deadly_infections_at_bay-178187
http://www.ebiotrade.com/newsf/2016-3/2016317131115664.htm

Marwick JA, Dorward DA, Lucas CD, Jones KO, Sheldrake TA, Fox S, Ward C, Murray J, Brittan M, Hirani N, Duffin R, Dransfield I, Haslett C, Rossi AG. Oxygen levels determine the ability of glucocorticoids to influence neutrophil survival in inflammatory environments. J Leukoc Biol. 2013 Dec;94(6):1285-92. doi: 10.1189/jlb.0912462. PubMed PMID: 23964116; PubMed Central PMCID: PMC3855024.

https://bionews-tx.com/news/2014/03/12/chronic-bronchitis-emphysema-lung-disease-drug-ineffectiveness-explained-in-new-study/
https://stv.tv/news/east-central/266592-new-treatment-for-lung-diseases-a-step-closer-after-breakthrough/
https://m.medicalxpress.com/news/2013-12-oxygen-decrease-effectiveness-anti-inflammatory-therapies.html

Wheatley PS, Butler AR, Crane MS, Fox S, Xiao B, Rossi AG, Megson IL, Morris RE. NO-releasing zeolites and their antithrombotic properties. J Am Chem Soc. 2006 Jan 18;128(2):502-9. PubMed PMID: 16402837.

https://www.newscientist.com/article/mg18524856-700-pollution-fighter-turns-clot-buster/

Fox S, Wilkinson TS, Wheatley PS, Xiao B, Morris RE, Sutherland A, Simpson AJ, Barlow PG, Butler AR, Megson IL, Rossi AG. NO-loaded Zn(2+)-exchanged zeolite materials: a potential bifunctional anti-bacterial strategy. Acta Biomater. 2010 Apr;6(4):1515-21. toi: 10.1016/j.actbio.2009.10.038. PubMed PMID: 19861185.

http://www.ed.ac.uk/news/all-news/superbugs-231109
https://www.healthcanal.com/medical-breakthroughs/4056-new-chemical-may-play-key-role-in-hospital-superbugs-battle.html


Duffin R, Leitch AE, Sheldrake TA, Hallett JM, Meyer C, Fox S, Alessandri AL, Martin MC, Brady HJ, Teixeira MM, Dransfield I, Haslett C, Rossi AG. The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1. FEBS Lett. 2009 Aug 6;583(15):2540-6. dos: 10.1016/j.febslet.2009.07.017. PubMed PMID: 19616548.

http://news.bbc.co.uk/1/hi/scotland/edinburgh_and_east/8403307.stm
https://www.sciencedaily.com/releases/2009/12/091209113846.htm
http://www.nursinginpractice.com/article/cancer-drug-may-work-asthma

Rossi AG, Sawatzky DA, Walker A, Ward C, Sheldrake TA, Riley NA, Caldicott A, Martinez-Losa M, Walker TR, Duffin R, Gray M, Crescenzi E, Martin MC, Brady HJ, Savill JS, Dransfield I, Haslett C. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med. 2006 Sep;12(9):1056-64.

https://www.sciencedaily.com/releases/2006/09/060903150749.htm
https://www.eurekalert.org/pub_releases/2006-09/uoe-kso090106.php


Mandal P, Chalmers JD, Graham C, Harley C, Sidhu MK, Doherty C, Govan JW, Sethi T, Davidson DJ, Rossi AG, Hill AT. Atorvastatin as a stable treatment in bronchiectasis: a randomised controlled trial. Lancet Respir Med. 2014 Jun;2(6):455-63. doi: 10.1016/S2213-2600(14)70050-5. PubMed PMID: 24717640.

http://timesofindia.indiatimes.com/india/Statins-may-help-lung-disease-patients-as-well/articleshow/32674629.cms
http://www.scotsman.com/news/health/statins-may-help-those-with-lung-conditions-1-3351544
https://www.nursingtimes.net/statins-could-help-lung-patients/5069233.article?blocktitle=News-archive&contentID=700
http://www.business-standard.com/article/news-ani/cholesterol-lowering-drug-statins-could-ease-coughing-in-lung-disease-patients-114032500284_1.html
http://www.dailymail.co.uk/news/article-2587635/Doctors-fears-statins-putting-lives-risk-Professor-says-unjustified-concerns-effects-mean-drugs-not-prescribed-enough.html
http://www.heraldscotland.com/news/13152003.Statins_shown_to_help_with_chronic_coughing/
http://www.scienceworldreport.com/articles/13653/20140325/statin-cholesterol-lowering-drug-offers-relief-from-chronic-lung-disease.htm
Year(s) Of Engagement Activity 2006,2009,2010,2013,2014,2016,2017
 
Description Phagocyte Workshop 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Participation in a Phagocyte Workshop with poster presentation and helpful discussions at poster session.
Year(s) Of Engagement Activity 2017
 
Description Phagocyte Workshop talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk at an international conference
Year(s) Of Engagement Activity 2016
 
Description invited seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Invited presentation about our science with subsequent Q&A session
Year(s) Of Engagement Activity 2016