| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Rossaint, Jan Nadler, Jerry L Ley, Klaus Zarbock, Alexander |
| Abstract | 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. |
| Related Links | https://ccforum.biomedcentral.com/counter/pdf/10.1186/cc11518.pdf |
| Ending Page | 15 |
| Page Count | 15 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 13648535 |
| DOI | 10.1186/cc11518 |
| Journal | Critical Care |
| Issue Number | 5 |
| Volume Number | 16 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2012-09-13 |
| Access Restriction | Open |
| Subject Keyword | Intensive Critical Care Medicine Emergency Medicine lipoxygenase acute lung injury inflammation leukocyte recruitment |
| Content Type | Text |
| Resource Type | Article |
| Subject | Critical Care and Intensive Care Medicine |
| Journal Impact Factor | 8.8/2023 |
| 5-Year Journal Impact Factor | 10.4/2023 |
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