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Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury
INTRODUCTION: Acute lung injury (ALI) is a common disease in critically ill patients with a high morbidity and mortality. 12/15-lipoxygenase (12/15-LO) is an enzyme generating 12-hydroxy-eicosatetraenoic acid (12-HETE) and 15-HETE from arachidonic acid. It has been shown that 12/15-LO is involved in...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682261/ https://www.ncbi.nlm.nih.gov/pubmed/22973824 http://dx.doi.org/10.1186/cc11518 |
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author | Rossaint, Jan Nadler, Jerry L Ley, Klaus Zarbock, Alexander |
author_facet | Rossaint, Jan Nadler, Jerry L Ley, Klaus Zarbock, Alexander |
author_sort | Rossaint, Jan |
collection | PubMed |
description | INTRODUCTION: Acute lung injury (ALI) is a common disease in critically ill patients with a high morbidity and mortality. 12/15-lipoxygenase (12/15-LO) is an enzyme generating 12-hydroxy-eicosatetraenoic acid (12-HETE) and 15-HETE from arachidonic acid. It has been shown that 12/15-LO is involved in the regulation of vascular permeability during ALI. METHODS: To test whether 12/15-LO participates in leukocyte recruitment into the lung, we investigated the role of 12/15-LO in mouse models of lipopolysaccharide (LPS)-induced pulmonary inflammation and acid-induced ALI, a clinically relevant model of acute lung injury. RESULTS: The increase in neutrophil recruitment following LPS inhalation was reduced in 12/15-LO-deficient (Alox15(-/-)) mice and in wild-type (WT) mice after the blocking of 12/15-LO with a pharmacological inhibitor. Bone marrow chimeras revealed that 12/15-LO in hematopoietic cells regulates neutrophil accumulation in the interstitial and alveolar compartments, whereas the accumulation of neutrophils in the intravascular compartment is regulated by 12/15-LO in non-hematopoietic and hematopoietic cells. Mechanistically, the increased plasma levels of the chemokine CXCL1 in Alox15(-/- )mice led to a reduced response of the neutrophil chemokine receptor CXCR2 to stimulation with CXCL1, which in turn abrogated neutrophil recruitment. Alox15(-/- )mice also showed decreased edema formation, reduced neutrophil recruitment and improved gas exchange in an acid-induced ALI model. CONCLUSIONS: Our findings suggest that 12/15-LO modulates neutrophil recruitment into the lung by regulating chemokine/chemokine receptor homeostasis. |
format | Online Article Text |
id | pubmed-3682261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36822612013-06-25 Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury Rossaint, Jan Nadler, Jerry L Ley, Klaus Zarbock, Alexander Crit Care Research INTRODUCTION: Acute lung injury (ALI) is a common disease in critically ill patients with a high morbidity and mortality. 12/15-lipoxygenase (12/15-LO) is an enzyme generating 12-hydroxy-eicosatetraenoic acid (12-HETE) and 15-HETE from arachidonic acid. It has been shown that 12/15-LO is involved in the regulation of vascular permeability during ALI. METHODS: To test whether 12/15-LO participates in leukocyte recruitment into the lung, we investigated the role of 12/15-LO in mouse models of lipopolysaccharide (LPS)-induced pulmonary inflammation and acid-induced ALI, a clinically relevant model of acute lung injury. RESULTS: The increase in neutrophil recruitment following LPS inhalation was reduced in 12/15-LO-deficient (Alox15(-/-)) mice and in wild-type (WT) mice after the blocking of 12/15-LO with a pharmacological inhibitor. Bone marrow chimeras revealed that 12/15-LO in hematopoietic cells regulates neutrophil accumulation in the interstitial and alveolar compartments, whereas the accumulation of neutrophils in the intravascular compartment is regulated by 12/15-LO in non-hematopoietic and hematopoietic cells. Mechanistically, the increased plasma levels of the chemokine CXCL1 in Alox15(-/- )mice led to a reduced response of the neutrophil chemokine receptor CXCR2 to stimulation with CXCL1, which in turn abrogated neutrophil recruitment. Alox15(-/- )mice also showed decreased edema formation, reduced neutrophil recruitment and improved gas exchange in an acid-induced ALI model. CONCLUSIONS: Our findings suggest that 12/15-LO modulates neutrophil recruitment into the lung by regulating chemokine/chemokine receptor homeostasis. BioMed Central 2012 2012-09-13 /pmc/articles/PMC3682261/ /pubmed/22973824 http://dx.doi.org/10.1186/cc11518 Text en Copyright ©2012 Rossaint et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Rossaint, Jan Nadler, Jerry L Ley, Klaus Zarbock, Alexander Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury |
title | Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury |
title_full | Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury |
title_fullStr | Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury |
title_full_unstemmed | Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury |
title_short | Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury |
title_sort | eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682261/ https://www.ncbi.nlm.nih.gov/pubmed/22973824 http://dx.doi.org/10.1186/cc11518 |
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