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. 2005 Jul 10;11(8):875–879. doi: 10.1038/nm1267

Figure 4. SARS-CoV Spike mediates lung injury through modulation of the renin-angiotensin system.

Figure 4

(a,b) Localization of intraperitoneally injected Spike(S-1190)-Fc in lung tissue. (a) Spike-Fc was detected by pull-down assay with Protein G Sepharose and western blot with human Fc–specific antibody. Mouse IgG is shown as loading control. (b) Lung immunohistochemistry to detect Spike(S-1190)-Fc or control-Fc protein using a human Fc–specific antibody. Spike(S-1190)-Fc localizes to bronchial epithelial cells (left; original magnification, ×100), inflammatory exudates cells (middle; original magnification, ×200), and alveolar pneumocytes (right; original magnification, ×200). (c) Decreased ACE2 protein expression in the lungs of Spike(S-1190)-Fc– treated mice. Lung homogenates were prepared from control-Fc– and Spike(S-1190)-Fc–treated wild-type mice and analyzed by western blot with ACE2-specific antibody. (d) AngII peptide levels in lungs of Spike(S1190)-Fc protein– or control–Fc-treated wild-type mice after saline or acid aspiration. AngII levels were determined at 3 h by enzyme immunoassay. Bars, mean ± s.e.m. *P < 0.05 comparing Spike(S1190)-Fc– and control-Fc–treated wild-type mice after acid injury. (e) Lung elastance measurements in acid plus Spike(S1190)-Fc–challenged wild-type mice treated with the AT1R inhibitor losartan (15 mg/kg). n = 4–6 per group. P < 0.05 comparing losartan-treated Spike(S1190)-Fc–challenged mice with vehicle-treated Spike(S1190)-Fc–challenged mice. (f) Wet to dry weight ratios of lungs of acid and Spike(S1190)-challenged mice in the presence or absence of losartan (15 mg/kg). n = 4–6 mice per group. *P < 0.05, comparing losartan-treated wild-type with vehicle-treated wild-type mice at 3 h after acid injury.