Leukotriene A(4) hydrolase inhibition attenuates allergic airway inflammation and hyperresponsiveness

American Journal of Respiratory and Critical Care Medicine
Navin L RaoPaul J Dunford

Abstract

Allergic asthma is characterized by reversible airway obstruction, lung inflammation, and airway hyperresponsiveness (AHR). Previous studies using leukotriene B(4) (LTB(4)) receptor 1-deficient mice and adoptive transfer experiments have suggested that LTB(4) plays a role in lung inflammation and AHR. In this study, we used a leukotriene A(4) hydrolase (LTA(4)H) inhibitor as a pharmacological tool to directly examine the role of LTB(4) in a mast cell-dependent murine model of allergic airway inflammation. We used the forced oscillation technique to test the effects of an LTA(4)H inhibitor dosed during the challenge phase on AHR. Lung tissue and lavage were collected for analysis. Treatment with an LTA(4)H inhibitor improved multiple parameters encompassing AHR and lung function. Significant decreases in inflammatory leukocytes, cytokines, and mucin were observed in the lung lumen. Serum levels of antigen-specific IgE and IgG1 were also decreased. Labeled antigen uptake by lung dendritic cells and subsequent trafficking to draining lymph nodes and the lung were decreased on LTA(4)H inhibitor treatment. Provocatively, inhibition of LTA(4)H increased lipoxin A(4) levels in lung lavage fluid. These data suggest that LTB(4) plays a ...Continue Reading

References

Jun 1, 1992·The American Review of Respiratory Disease·P E ChristieT H Lee
Jan 1, 1988·Advances in Experimental Medicine and Biology·S E DahlénC A Veale
Oct 1, 1996·The Journal of Experimental Medicine·W R HendersonE Y Chi
Mar 25, 1998·Current Biology : CB·G J McKenzieA N McKenzie
Sep 22, 1998·The Journal of Experimental Medicine·W W HuangA D Luster
Aug 10, 2000·The Journal of Experimental Medicine·C M Williams, S J Galli
Jan 9, 2001·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·N BeckmannJ R Fozard
Jun 28, 2001·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·R A NathanUNKNOWN Antileukotriene Working Group
Dec 12, 2001·American Journal of Respiratory and Critical Care Medicine·M L SeymourA P Sampson
Apr 10, 2002·The Journal of Allergy and Clinical Immunology·Paolo Montuschi, Peter J Barnes
Jun 13, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nicolau BeckmannJohn R Fozard
Jun 19, 2002·Journal of Applied Physiology·Shinichiro TomiokaCharles G Irvin
Aug 3, 2002·American Journal of Respiratory and Critical Care Medicine·Adam AntczakPeter J Barnes
Mar 11, 2003·Journal of Applied Physiology·Jason H T Bates, Charles G Irvin
May 20, 2003·Advances in Experimental Medicine and Biology·Bruce D LevyCharles N Serhan
May 27, 2003·The Journal of Asthma : Official Journal of the Association for the Care of Asthma·Masafumi ZaitsuEiichi Ishii
Sep 2, 2003·Nature Immunology·Andrew M TagerAndrew D Luster
Sep 2, 2003·Nature Immunology·Katayoon GoodarziUlrich H von Andrian
Feb 10, 2004·The Journal of Allergy and Clinical Immunology·Stefania ZanconatoEugenio Baraldi
Nov 26, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Seok-Yong EumJames G Martin
Jan 13, 2005·The Journal of Pharmacology and Experimental Therapeutics·Gaoyun YangAnuk M Das
Mar 23, 2005·The Journal of Experimental Medicine·Leonie S van RijtBart N Lambrecht
Apr 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nobuaki MiyaharaErwin W Gelfand
Apr 26, 2005·American Journal of Respiratory and Critical Care Medicine·Nobuaki MiyaharaErwin W Gelfand
Jun 16, 2005·The Journal of Experimental Medicine·Charlotte L WellerTimothy J Williams
Sep 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kan TerawakiTakao Shimizu
Nov 19, 2005·American Journal of Respiratory and Critical Care Medicine·John J LimaKathleen Barnes
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christian TaubeErwin W Gelfand
Mar 7, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claudia JakubzickGwendalyn J Randolph
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paul J DunfordRobin L Thurmond
Jul 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthew E WikstromPhilip A Stumbles
Nov 1, 2006·Allergology International : Official Journal of the Japanese Society of Allergology·Nobuaki MiyaharaErwin W Gelfand
Jan 4, 2007·The Journal of Clinical Investigation·Frank TackeGwendalyn J Randolph
Jan 6, 2007·American Journal of Respiratory and Critical Care Medicine·Paul ForsytheJohn Bienenstock
Jan 27, 2007·American Journal of Respiratory and Critical Care Medicine·Lennart K A LundbladJason H T Bates
Mar 21, 2007·The Journal of Pharmacology and Experimental Therapeutics·Navin L RaoAnne M Fourie
Mar 31, 2007·International Journal of Clinical Practice·W BergerC B Cairns
May 29, 2007·The Journal of Asthma : Official Journal of the Association for the Care of Asthma·Sally WenzelJudith Harris
Nov 26, 2008·American Journal of Respiratory Cell and Molecular Biology·Nobuaki MiyaharaErwin W Gelfand
Oct 16, 2013·Annals of the Rheumatic Diseases·Jeffery M CowdenRobin L Thurmond

❮ Previous
Next ❯

Citations

Sep 23, 2011·Chemical Reviews·Jesper Z Haeggström, Colin D Funk
Nov 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Antonio Di GennaroJesper Z Haeggström
Aug 30, 2013·Science Translational Medicine·Wen TianMark R Nicolls
Aug 2, 2011·American Journal of Respiratory and Critical Care Medicine·Shamsah Kazani, Elliot Israel
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Alena StsiapanavaJesper Z Haeggström
Jun 12, 2013·Paediatric Drugs·Paul D Robinson, Peter Van Asperen
Sep 25, 2014·Archives of Toxicology·Ahmed A El-Sherbeni, Ayman O S El-Kadi
Dec 20, 2013·Expert Opinion on Pharmacotherapy·Hiroto Matsuse, Shigeru Kohno
Jun 2, 2010·Pharmaceuticals·Paolo Montuschi
Dec 27, 2011·The Journal of Allergy and Clinical Immunology·Peter J Barnes
Jun 21, 2011·Advanced Drug Delivery Reviews·Ivy Pal, Joshua D Ramsey
May 25, 2010·Biochemical and Biophysical Research Communications·Jesper Z HaeggströmAnders Wetterholm
Jul 7, 2015·Annals of the American Thoracic Society·Theodore J TorphyUNKNOWN Antiinflammatory Therapy Working Group
Apr 15, 2015·Respirology : Official Journal of the Asian Pacific Society of Respirology·Wei GaoXin Yao
Oct 5, 2013·Expert Opinion on Therapeutic Targets·Antonio Di Gennaro, Jesper Z Haeggström
Mar 18, 2017·Scientific Reports·Caroline M LowRobert J Snelgrove
Nov 5, 2014·Journal of Medicinal Chemistry·Olivier Corminboeuf, Xavier Leroy
Nov 26, 2010·JRSM Short Reports·Cinzia PapadiaAlastair Forbes
Nov 10, 2010·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·P Montuschi, M L Peters-Golden
Sep 14, 2010·The Journal of Asthma : Official Journal of the Association for the Care of Asthma·Jason Yongha KimHyoung Doo Shin
Feb 18, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators
Nov 13, 2019·Pediatric Pulmonology·Lucy Perrem, Felix Ratjen
Jun 21, 2019·Science Translational Medicine·Dhiren F PatelRobert J Snelgrove
Aug 21, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christoph LehmannAstrid Stefanie Kahnt
Aug 16, 2018·The Journal of Clinical Investigation·Jesper Z Haeggström
Jun 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Suaad A AudatQosay A Al-Balas
Oct 30, 2016·Clinical and Translational Science·J S ElbornE B Springman
Jan 6, 2017·Journal of Lipid Research·Yan ZhangCharles R Brown
Feb 13, 2018·Immunological Reviews·Piper A RobidaBruce S Bochner
Jan 14, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lotte M SchmidtAlexander H Dalpke
Oct 6, 2020·Frontiers in Pharmacology·Lucy Perrem, Felix Ratjen
Oct 29, 2020·Signal Transduction and Targeted Therapy·Cuixue WangHai Tian
Jul 24, 2021·Journal of Pharmacological Sciences·Tatsuro Nakamura
Sep 23, 2021·PloS One·Cyrielle MaroteauUNKNOWN PiCA Consortium
Aug 24, 2018·Science Translational Medicine·Dhiren F PatelRobert J Snelgrove

❮ Previous
Next ❯

Related Concepts

Related Feeds

Asthma

This feed focuses in Asthma in which your airways narrow and swell. This can make breathing difficult and trigger coughing, wheezing and shortness of breath.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

American Thoracic Association Journals

Discover the latest respiratory research published by the journals from the American Thoracic Society.