Fig. 4

Protective effects of ONO-4641 treatment against elastase-induced emphysema in mice. Mice were intratracheally injected with 5 U of porcine pancreatic elastase. ONO-4641 (0.3 mg/kg) or vehicle was intragastrically injected at 1 h before elastase injection, and then every 24 h for consecutive 14 days. a Representative micro-CT images of lung cross-sections in a mouse model of elastase-induced emphysema treated with vehicle or ONO-4641 (Day 28); the low-attenuation areas (LAAs, less than −700 Hounsfield units) are presented in blue. b LAA percentage in mice with elastase or PBS-treated emphysema that were administered vehicle or ONO-4641 at the indicated time points (n = 6−8 in the elastase-treated group, n = 5 in the PBS-treated group). Data are presented as the mean ± SEM. **P < 0.01. c Histopathological examination of lung specimens from mice with elastase-treated emphysema that were administered vehicle or ONO-4641 (Day 28). Scale bar, 250 μm (d) Mean linear intercepts (Lm) were determined as the average of 10 randomly selected fields of each lung obtained from vehicle-treated or ONO-4641-treated mice 28 days after elastase or PBS injection (n = 5 in elastase-treated group, n = 4 in PBS-treated group). Data are presented as the mean ± SEM. *P < 0.05. e, f Numbers of total cells, neutrophils, macrophages (e), and levels of TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 (f) in BALF at the indicated time points after elastase injection (n = 6−8 in elastase-treated group, n = 4–5 in PBS-treated group). Data are presented as the mean ± SEM. *P < 0.05. g Representative dual staining for tomato lectin and MMP-12 in the lungs of mice with elastase-treated emphysema that were administered vehicle or ONO-4641 (Day 7). Scale bar, 50 μm. h−j Representative two-parameter histograms (h), quantification of CD11b⁺Gr-1⁺ cells including Ly-6C⁺ and Ly-6G⁺ cells (i), and quantification of lymphocytes (j) in the lungs from mice intragastrically treated with vehicle or ONO-4641 (0.3 mg/kg) once a day for 7 days after elastase injection (n = 5 in each group). Data are presented as the mean ± SEM. ***P < 0.001. k, l Histopathological examination of lung specimens (k) and Lm (l) in elastase-treated mice 28 days after intravenous adoptive transfer of PBS, or vehicle-treated or ONO-4641-expanded CD11b⁺Gr-1⁺ cells (n = 6 or 7 in each group). m, n Numbers of total cells, neutrophils, and macrophages (m), and levels of TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 (n) in BALF at the indicated time points after elastase injection with adaptive transfer of vehicle-treated or ONO-4641-expanded CD11b⁺Gr-1⁺ cells (n = 3−5). Data are presented as the mean ± SEM. *P < 0.05. ***P < 0.001