Expression of the human integrin β 6 subunit in alveolar type II cells and bronchiolar epithelial cells reverses lung inflammation in β 6 knockout mice

X Huang, J Wu, W Zhu, R Pytela… - American journal of …, 1998 - atsjournals.org
X Huang, J Wu, W Zhu, R Pytela, D Sheppard
American journal of respiratory cell and molecular biology, 1998atsjournals.org
Inactivation of the integrin β6 subunit gene in mice resulted in an unexpected phenotype—
functionally significant inflammation of the skin and lungs. These findings suggested a role
for ligation of the αvβ6 integrin on epithelial cells in downregulating epithelial inflammation.
However, the results of gene inactivation could have been due to inactivation of adjacent
genes and provided no information about the role of this integrin in specific populations of
epithelial cells. In the current study, we used transgenic mice constitutively expressing the …
Inactivation of the integrin β6 subunit gene in mice resulted in an unexpected phenotype—functionally significant inflammation of the skin and lungs. These findings suggested a role for ligation of the αvβ6 integrin on epithelial cells in downregulating epithelial inflammation. However, the results of gene inactivation could have been due to inactivation of adjacent genes and provided no information about the role of this integrin in specific populations of epithelial cells. In the current study, we used transgenic mice constitutively expressing the human β6 subunit in alveolar type II cells and bronchiolar epithelial cells to examine directly the significance of αvβ6 in these cells. Expression of this transgene largely inhibited the increases in airspace lymphocytes and macrophages and the lymphocyte and macrophage activation caused by inactivation of the β6 subunit gene, and reduced the peribronchial and perivascular accumulations of lymphocytes. In the genetically mixed mice used for this study, we identified airway eosinophilia as an additional effect of β6 inactivation. This effect was also partially inhibited by limited expression of the human transgene. These results definitively identify a role for distal lung epithelial αvβ6 in downregulating pulmonary inflammation and suggest that interventions augmenting β6 expression or function in these cells could influence the course of inflammatory lung diseases.
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