| Title | Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4). | | Author(s) | Levy BD, De Sanctis GT, Devchand PR, Kim E, Ackerman K, Schmidt BA, Szczeklik W, Drazen JM, Serhan CN | | Institution | Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. | | Source | Nat Med 2002 Sep; 8(9):1018-23. | | MeSH | Animals
Asthma
Bronchial Hyperreactivity
Bronchitis
Chemokines, CC
Eosinophils
Hydroxyeicosatetraenoic Acids
Interleukin-13
Interleukin-5
Leukotrienes
Lipoxins
Male
Methacholine Chloride
Mice
Mice, Inbred BALB C
Mice, Transgenic
Prostaglandins
Receptors, Cell Surface
Receptors, Formyl Peptide
Receptors, Lipoxin
Research Support, U.S. Gov't, P.H.S.
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12172542 |
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