Asset Details
Do you wish to reserve the book?
15-Epi-lipoxin A4 Inhibits Myeloperoxidase Signaling and Enhances Resolution of Acute Lung Injury
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
15-Epi-lipoxin A4 Inhibits Myeloperoxidase Signaling and Enhances Resolution of Acute Lung Injury
Do you wish to request the book?
15-Epi-lipoxin A4 Inhibits Myeloperoxidase Signaling and Enhances Resolution of Acute Lung Injury
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
15-Epi-lipoxin A4 Inhibits Myeloperoxidase Signaling and Enhances Resolution of Acute Lung Injury
2009
Overview
Abstract
Rationale
Apoptosis is essential for removal of neutrophils from inflamed tissues and efficient resolution of inflammation. Myeloperoxidase (MPO), abundantly expressed in neutrophils, not only generates cytotoxic oxidants but also signals through the β2 integrin Mac-1 to rescue neutrophils from constitutive apoptosis, thereby prolonging inflammation.
Objectives
Because aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4) modulates Mac-1 expression, we investigated the impact of 15-epi-LXA4 on MPO suppression of neutrophil apoptosis and MPO-mediated neutrophil-dependent acute lung injury.
Methods
Human neutrophils were cultured with MPO with or without 15-epi-LXA4 to investigate development of apoptosis. Acute lung injury was produced by intratracheal injection of carrageenan plus MPO or intraperitoneal injection of live Escherichia coli in mice, and the animals were treated with 15-epi-LXA4 at the peak of inflammation.
Measurements and Main Results
15-Epi-LXA4 through down-regulation of Mac-1 expression promoted apoptosis of human neutrophils by attenuating MPO-induced activation of extracellular signal–regulated kinase and Akt-mediated phosphorylation of Bad and by reducing expression of the antiapoptotic protein Mcl-1, thereby aggravating mitochondrial dysfunction. The proapoptotic effect of 15-epi-LXA4 was dominant over MPO-mediated effects even when it was added at 4 hours post MPO. In mice, treatment with 15-epi-LXA4 accelerated the resolution of established carrageenan plus MPO-evoked as well as E. coli–induced neutrophil-dependent pulmonary inflammation through redirecting neutrophils to caspase-mediated cell death and facilitating their removal by macrophages.
Conclusions
These results demonstrate that aspirin-triggered 15-epi-LXA4 enhances resolution of inflammation by overriding the powerful antiapoptosis signal from MPO, thereby demonstrating a hitherto unrecognized mechanism by which aspirin promotes resolution of inflammation.
Publisher
Am Thoracic Soc,Oxford University Press,American Thoracic Society
Subject
Acute Lung Injury - immunology
/ Acute Lung Injury - pathology
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Animals
/ Anti-Inflammatory Agents, Non-Steroidal - pharmacology
/ Aspirin
/ Biological and medical sciences
/ Bronchoalveolar Lavage Fluid - immunology
/ Emergency and intensive respiratory care
/ Female
/ Humans
/ Kinases
/ Mice
