Beta 7 Integrins Are Necessary For The Development Of Airway Hyper-Responsiveness, But Not Airway Inflammation, In A Murine Model Of Asthma.

R.V. Venkayya, D.B. Corry, N. Wagner, W. Muller, D.J. Erle,


The íŸ7 integrins, [alpha]4íŸ7 and [alpha]EíŸ7, are adhesion molecules expressed on lymphocytes and other leukocytes. [alpha]4íŸ7 binds to MAdCAM-1 and VCAM-1 on endothelial cells, and to fibronectin in the extracellular matrix. [alpha]EíŸ7 binds to an epithelial cell surface protein, E-cadherin. We used íŸ7-deficient (íŸ7^{-/-}) mice to characterize the role of íŸ7 integrins in the pathophysiology of airway inflammation and hyperresponsiveness. íŸ7^{+/+} and íŸ7^{-/-} C57BL/6 mice were sensitized and challenged intratracheally with antigen (Aspergillus extract) or saline. Mice were paralyzed and mechanically ventilated, and acetylcholine-induced changes in airway resistance were measured by plethysmography. íŸ7^{+/+} mice that received antigen developed hyperresponsiveness to acetylcholine, but íŸ7^{-/-} mice did not. Analysis of bronchoalveolar lavage and lung leukocytes showed that antigen administration induced similar accumulations of inflammatory cells (including lymphocytes and eosinophils) in íŸ7^{+/+} and íŸ7^{-/-} mice. We conclude that [alpha]4íŸ7 and/or [alpha]EíŸ7 play a role in the development of airway hyperresponsiveness in this model, but íŸ7 integrins are not required for cellular recruitment to the airways. Since integrins are coupled to intracellular signaling pathways, it is possible that íŸ7-mediated signals play a role in the development of airway hyperresponsiveness.

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The American Lung Association - American Thoracic Association Conference,1998
    • ALA-ATA