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Figure 2. The protective effect of HO-1 during hyperoxia is dependent on endothelial STAT3 in vivo. A) Endothelial-targeted STAT3-deficient (STAT3E–/–) mice were administered intranasal rat HO-1 gene in an adenoviral vector (Ad-HO-1, 5x108 plaque-forming units) and lung lysates were obtained after 48 h. Lung lysates were immunoblotted against HO-1 or ß-tubulin (loading control). B) STAT3E–/–mice were exposed to 72 h O2 after intranasal administration of Ad-HO-1 (5x108 plaque-forming units). Lung lysates were immunoblotted against HO-1 or ß-tubulin. C) Percent survival of STAT3 WT and STAT3E–/–mice administered Ad-null or Ad-HO-1, then exposed to continuous O2 (n=8–15). *P < 0.05 compared with STAT3 WT Ad-HO-1 / O2. D) Lung permeability was assessed by BAL protein content in naive STAT3E–/– and STAT3E–/– mice administered Ad-null or Ad-HO-1, then exposed to 72 h O2 (n=3–5). Data are shown as mean ± SE. *P < 0.05 compared with Ad-null/O2 and Ad-HO-1/O2 mice. E) Lung inflammation was detected by BAL cell counts in naive STAT3E–/– and STAT3E–/– mice given Ad-null or Ad-HO-1, then exposed to 72 h O2 (n=3–5). Data are shown as mean ± SE. *P < 0.05 compared with Ad-null/O2 and Ad-HO-1/O2 mice. F) TUNEL quantitation was expressed as % of total cells in lung sections from naive STAT3E–/– and STAT3E–/– mice given Ad-null or Ad-HO-1, then exposed to 72 h O2 (n=3–5). Data are shown as mean ± SE. *P < 0.05 compared with Ad-null/O2 and Ad-HO-1/O2.
