Mice Lacking 12/15-Lipoxygenase have Attenuated Airway Allergic Inflammation and Remodeling.
Andersson, Cecilia LU ; Claesson, Hans-Erik ; Rydell-Törmänen, Kristina LU
; Swedmark, Stellan
; Hallgren, Anneli
and Erjefält, Jonas
LU
(2008)
In American Journal of Respiratory Cell and Molecular Biology
39(6).
p.648-656
- Abstract
- Arachidonate 15-lipoxygenase (LO)-1 has been implicated in allergic inflammation and asthma. The overall effect of 15-LO in allergic inflammation in vivo is, however, unclear. This study investigates systemic allergen sensitization and local allergic airway inflammation and remodeling in mice lacking the murine 12/15-LO, the ortholog to human 15-LO-1. Upon systemic sensitization with intraperitoneal ovalbumin, 12/15 LO(-/-) mice produced elevated levels of allergen-specific IgE compared to wild type (Wt) controls. However, when challenged with repeated aerosolized allergen sensitized 12/15 LO(-/-) mice had an impaired development of airway allergic inflammation compared to Wt controls, as indicated by reduced BAL fluid leukocytes... (More)
- Arachidonate 15-lipoxygenase (LO)-1 has been implicated in allergic inflammation and asthma. The overall effect of 15-LO in allergic inflammation in vivo is, however, unclear. This study investigates systemic allergen sensitization and local allergic airway inflammation and remodeling in mice lacking the murine 12/15-LO, the ortholog to human 15-LO-1. Upon systemic sensitization with intraperitoneal ovalbumin, 12/15 LO(-/-) mice produced elevated levels of allergen-specific IgE compared to wild type (Wt) controls. However, when challenged with repeated aerosolized allergen sensitized 12/15 LO(-/-) mice had an impaired development of airway allergic inflammation compared to Wt controls, as indicated by reduced BAL fluid leukocytes (eosinophils, lymphocytes macrophages) and Th2 cytokines (IL-4, IL-5, IL-13) as well as tissue eosinophils. Allergen-induced airway epithelial proliferation was also significantly attenuated in 12/15 LO(-/-) mice whereas goblet cell hyperplasia was unaffected. However, 12/15 LO(-/-) mice had significantly reduced luminal mucus secretions compared to Wt controls. The repeated allergen challenges resulted in a dramatic increase of alpha-smooth muscle-actin positive alveolar cells in the peripheral airways, a phenomenon that was significantly less developed in 12/15 LO(-/-) mice. In conclusion, our data suggest that 12/15 LO(-/-) mice, although having a fully developed systemic sensitization, did not establish a fully developed allergic airway inflammation and associated manifestations of central and peripheral airway remodeling. These data suggest that 12/15-LO derived metabolites play an important pathophysiological role in allergen-induced inflammation and remodeling. Hence, pharmacologic targeting of the human 15-LO-1 may represent an attractive therapeutic strategy to control inflammation and remodeling in asthma. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1153677
- author
- Andersson, Cecilia
LU
; Claesson, Hans-Erik
; Rydell-Törmänen, Kristina
LU
; Swedmark, Stellan
; Hallgren, Anneli
and Erjefält, Jonas
LU
- organization
- publishing date
- 2008-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Allergens, Animals, Antibodies, Antibody Specificity, Apoptosis, Arachidonate 12-Lipoxygenase, Arachidonate 15-Lipoxygenase, Caspase 3, Cell Count, Cytokines, Eosinophilia, Goblet Cells, Hyperplasia, Hypersensitivity, Immunization, Inflammation, Leukocytes, Lung, Mice, Mice, Inbred C57BL, Ovalbumin, Journal Article, Research Support, Non-U.S. Gov't
- in
- American Journal of Respiratory Cell and Molecular Biology
- volume
- 39
- issue
- 6
- pages
- 9 pages
- publisher
- American Thoracic Society
- external identifiers
-
- wos:000261259500004
- pmid:18511709
- scopus:57349164262
- pmid:18511709
- ISSN
- 1535-4989
- DOI
- 10.1165/rcmb.2007-0443OC
- language
- English
- LU publication?
- yes
- id
- db1b4c59-25bf-4e03-a723-2123de661d8b (old id 1153677)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18511709?dopt=Abstract
- date added to LUP
- 2016-04-04 08:50:06
- date last changed
- 2022-04-23 18:04:38
@article{db1b4c59-25bf-4e03-a723-2123de661d8b,
abstract = {{Arachidonate 15-lipoxygenase (LO)-1 has been implicated in allergic inflammation and asthma. The overall effect of 15-LO in allergic inflammation in vivo is, however, unclear. This study investigates systemic allergen sensitization and local allergic airway inflammation and remodeling in mice lacking the murine 12/15-LO, the ortholog to human 15-LO-1. Upon systemic sensitization with intraperitoneal ovalbumin, 12/15 LO(-/-) mice produced elevated levels of allergen-specific IgE compared to wild type (Wt) controls. However, when challenged with repeated aerosolized allergen sensitized 12/15 LO(-/-) mice had an impaired development of airway allergic inflammation compared to Wt controls, as indicated by reduced BAL fluid leukocytes (eosinophils, lymphocytes macrophages) and Th2 cytokines (IL-4, IL-5, IL-13) as well as tissue eosinophils. Allergen-induced airway epithelial proliferation was also significantly attenuated in 12/15 LO(-/-) mice whereas goblet cell hyperplasia was unaffected. However, 12/15 LO(-/-) mice had significantly reduced luminal mucus secretions compared to Wt controls. The repeated allergen challenges resulted in a dramatic increase of alpha-smooth muscle-actin positive alveolar cells in the peripheral airways, a phenomenon that was significantly less developed in 12/15 LO(-/-) mice. In conclusion, our data suggest that 12/15 LO(-/-) mice, although having a fully developed systemic sensitization, did not establish a fully developed allergic airway inflammation and associated manifestations of central and peripheral airway remodeling. These data suggest that 12/15-LO derived metabolites play an important pathophysiological role in allergen-induced inflammation and remodeling. Hence, pharmacologic targeting of the human 15-LO-1 may represent an attractive therapeutic strategy to control inflammation and remodeling in asthma.}},
author = {{Andersson, Cecilia and Claesson, Hans-Erik and Rydell-Törmänen, Kristina and Swedmark, Stellan and Hallgren, Anneli and Erjefält, Jonas}},
issn = {{1535-4989}},
keywords = {{Allergens; Animals; Antibodies; Antibody Specificity; Apoptosis; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Caspase 3; Cell Count; Cytokines; Eosinophilia; Goblet Cells; Hyperplasia; Hypersensitivity; Immunization; Inflammation; Leukocytes; Lung; Mice; Mice, Inbred C57BL; Ovalbumin; Journal Article; Research Support, Non-U.S. Gov't}},
language = {{eng}},
number = {{6}},
pages = {{648--656}},
publisher = {{American Thoracic Society}},
series = {{American Journal of Respiratory Cell and Molecular Biology}},
title = {{Mice Lacking 12/15-Lipoxygenase have Attenuated Airway Allergic Inflammation and Remodeling.}},
url = {{http://dx.doi.org/10.1165/rcmb.2007-0443OC}},
doi = {{10.1165/rcmb.2007-0443OC}},
volume = {{39}},
year = {{2008}},
}