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.
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.
Organisations
- University of Edinburgh (Lead Research Organisation)
- Tokyo Medical and Dental University (Collaboration)
- University Hospital of Laval University (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
- University of Turku (Collaboration)
- University of Bristol (Collaboration)
- Beatson Institute for Cancer Research (Collaboration)
Publications
McCormick B
(2019)
A Negative Feedback Loop Regulates Integrin Inactivation and Promotes Neutrophil Recruitment to Inflammatory Sites.
in Journal of immunology (Baltimore, Md. : 1950)
Michael M
(2019)
A neutrophil-centric view of chemotaxis.
in Essays in biochemistry
McCormick B
(2019)
Cross-talk between Rho GTPases and PI3K in the neutrophil.
in Small GTPases
Chu JY
(2019)
HoxB8 neutrophils replicate Fc? receptor and integrin-induced neutrophil signaling and functions.
in Journal of leukocyte biology
Vermeren S
(2018)
Immune complex-induced neutrophil functions: A focus on cell death.
in European journal of clinical investigation
Chu JY
(2016)
Non-canonical PI3K-Cdc42-Pak-Mek-Erk Signaling Promotes Immune-Complex-Induced Apoptosis in Human Neutrophils.
in Cell reports
Parnham, MJ
(2019)
Principles of Immunopharmacology
Chu JY
(2018)
Small GTPase-dependent regulation of leukocyte-endothelial interactions in inflammation.
in Biochemical Society transactions
Michael M
(2021)
The 5-Phosphatase SHIP2 Promotes Neutrophil Chemotaxis and Recruitment.
in Frontiers in immunology
Killick J
(2020)
Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis.
in Frontiers in immunology
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) We published a paper together (Michael et al 2021, see publications). |
Start Year | 2016 |
Description | Collaboration with Inge Hers, Bristol |
Organisation | University of Bristol |
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 | 2016 |
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; help with imaging and image analysis |
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 | this collaborator provided valuable reagents that made our research possible. |
Impact | We published a paper together (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 |