A Conditional Lung Injury Model
|The lung tissue sections were stained with HE.|
Macrophages and alveolar epithelial type II (AE2) cells express the lysozyme M (LysM) gene. B6;129-Lyz2tm1(DTR)Mtka (LysM-DTR) mice were generated by targeting the LysMgene with a construct containing the human diphtheria toxin (DT) receptor (DTR) and heparin-binding epidermal growth factor-like growth factor in exon 1 of LysM. This transgenic mouse can serve as a toxin receptor-mediated conditional cell knockout model of acute respiratory distress syndrome by specifically deleting AE2 cells and alveolar macrophages after DT treatment. When DT is administered to these mice, they suffer from acute lung injury and die within 4 days. The amount of surfactant proteins in bronchoalveolar lavage fluid is significantly decreased in these DT-treated LysM-DTR mice. A transplantation of wild-type bone marrow cells to irradiated LysM-DTR mice can restore macrophages resistant to DT, thereby selectively deleting AE2 cells by DT administration. These conditional models are useful to clarify the roles of macrophages and AE2 cells in non-inflammatory lung injury.
|Depositor||:||Dr. Masato Tanaka, RIKEN Research Center for Allergy and Immunology|
|Reference||:||Miyake, Y., H. Kaise, K. Isono, H. Koseki, K. Kohno, and M. Tanaka. Protective role of macrophages in noninflammatory lung injury caused by selective ablation of alveolar epithelial type II cells. J. Immunol. 178:5001-5009 (2007).|