Figure 1. Deletion of β₁ integrin in AT2 cells results in increased inflammation, abnormal repair, and decreased survival after LPS-induced injury.

(A) Representative images of lung histology demonstrate increased edema at 3 and 7 days postinjury in β₁^AT2-KO lungs compared with β₁^fl/fl lungs, as well as persistent inflammation and emphysematous remodeling in β₁^AT2-KO lungs by 21 days post-LPS. D3, D7, and D21 refer to 3, 7, and 21 days after LPS injury, respectively. (B) Mean linear intercept quantified emphysematous alveolar remodeling at 21 days after LPS, 28.5 ± 0.9 μm in β₁^fl/fl lungs versus 40.2 ± 2.8 μm in β₁^AT2-KO lungs (n = 6–7 mice/group, P = 0.0014 by 2-tailed t test). (C) Bicinchoninic acid (BCA) protein assay quantified increased bronchoalveolar lavage (BAL) fluid protein in uninjured β₁^AT2-KO lungs and at 3 and 7 days post-LPS injury in β₁^AT2-KO lungs compared with β₁^fl/fl lungs at the same time points (n = 6–14 mice/group, 2-tailed t test comparing genotypes at each time point, P = 0.0485 for uninjured mice; P = 0.0036 at D3; P = 0.005 at D7; P = 0.2628 at D21). (D) BAL cell counts are significantly increased in β₁^AT2-KO lungs compared with β₁^fl/fl littermates in uninjured mice and at 7 and 21 days post-LPS. Peak inflammation is present at 7 days in β₁^AT2-KO lungs, 55,663 ± 3,306 cells/mL in β₁^fl/fl BAL fluid versus 624,000 ± 118,753 cells/mL in β₁^AT2-KO BAL (n = 6–26 mice/group, 2-tailed t test comparing genotypes at each time point, P = 0.0002 for uninjured mice; P = 0.0730 at D3; P = 0.0007 at D7; P < 0.0001 at D21). Total numbers of BAL fluid macrophages are significantly increased in uninjured β₁^AT2-KO mice and at D7 and D21; lymphocytes and neutrophils are significantly increased in β₁^AT2-KO BAL at D7 only. Scale bar = 50 μm for A. * P < 0.05.