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

Nature Medicine, ISSN: 1078-8956, Vol: 8, Issue: 9, Page: 1018-1023
2002
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Article Description

The prevalence of asthma continues to increase and its optimal treatment remains a challenge. Here, we investigated the actions of lipoxin A (LXA) and its leukocyte receptor in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated airway biosynthesis of LXA and increased expression of its receptor. Administration of a stable analog of LXA 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 LXA 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 LXA analog highlights a unique counter- regulatory profile for the LXA 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.

Bibliographic Details

Levy, Bruce D.; De Sanctis, George T.; Devchand, Pallavi R.; Kim, Eugene; Ackerman, Kate; Schmidt, Birgitta A.; Szczeklik, Wojciech; Drazen, Jeffrey M.; Serhan, Charles N.

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

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