Figure 4.

Nox2 activity during coinfection exacerbates tissue damage. (A–C) WT and Nox2-deficient (KO) mice were infected with PR8 and 7 d later superchallenged with MRSA. BALFs were analyzed for albumin and LDH levels at days 1 (A), 3 (B), and 6 (C) after infection. Data represent albumin and LDH levels relative to these in naive WT mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001, Tukey's multiple comparisons test. (D and E) At 6 dpi, lungs were analyzed for histopathology (H&E; D) and histopathologic scores (each symbol represents one mouse; E). (E) Whole mount H&E-stained sections of lung tissue from each mouse were semiquantitatively assessed at low power (100×) for the proportion of parenchyma with alveoli-containing intraluminal material (proteinaceous exudate and/or fibrin) in the background of interstitial expansion and inflammation. Each lung was scored by the relative amount of abnormal tissue as follows: normal = 0; 1–25% = 1; 26–50% = 2; 51–75% = 3; >76% = 4. ***, P < 0.001, Student’s t test. Bars, 100 µm. All PR8-infected (Flu), MRSA-infected (MRSA), or coinfected mice (Flu + MRSA) were treated daily with linezolid until 24 h before harvesting the samples. Data shown in (A–D) are representative of two independent experiments. Data shown in E were combined from two independent experiments.