Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4 Academic Article uri icon

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abstract

  • The prevalence of asthma continues to increase and its optimal treatment remains a challenge. Here, we investigated the actions of lipoxin A(4) (LXA(4)) and its leukocyte receptor in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated airway biosynthesis of LXA(4) and increased expression of its receptor. Administration of a stable analog of LXA(4) 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(4) 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(4) analog highlights a unique counter-regulatory profile for the LXA(4) 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.

authors

  • 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

publication date

  • September 2002

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