Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4

BD Levy, GT De Sanctis, PR Devchand, E Kim… - Nature medicine, 2002 - nature.com
BD Levy, GT De Sanctis, PR Devchand, E Kim, K Ackerman, BA Schmidt, W Szczeklik
Nature medicine, 2002nature.com
The prevalence of asthma continues to increase and its optimal treatment remains a
challenge. Here, we investigated the actions of lipoxin A4 (LXA4) and its leukocyte receptor
in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated
airway biosynthesis of LXA4 and increased expression of its receptor. Administration of a
stable analog of LXA4 blocked both airway hyper-responsiveness and pulmonary
inflammation, as shown by decreased leukocytes and mediators, including interleukin-5 …
Abstract
The prevalence of asthma continues to increase and its optimal treatment remains a challenge. Here, we investigated the actions of lipoxin A4 (LXA4) and its leukocyte receptor in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated airway biosynthesis of LXA4 and increased expression of its receptor. Administration of a stable analog of LXA4 blocked both airway hyper-responsiveness and pulmonary inflammation, as shown by decreased leukocytes and mediators, including interleukin-5, interleukin-13, eotaxin, prostanoids and cysteinyl leukotrienes. Moreover, transgenic expression of human LXA4 receptors in murine leukocytes led to significant inhibition of pulmonary inflammation and eicosanoid-initiated eosinophil tissue infiltration. Inhibition of airway hyper-responsiveness and allergic airway inflammation with a stable LXA4 analog highlights a unique counter-regulatory profile for the LXA4 system and its leukocyte receptor in airway responses. Moreover, our findings suggest that lipoxin and related pathways offer novel multi-pronged therapeutic approaches for human asthma.
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