Fig. 2. B5 blocks airway inflammation and fibrosis induced by cigarette smoke and the viral mimetic poly(I:C).

(A) Schematic showing creation of the cigarette smoke intranasal (IN)–poly(I:C)–induced mouse model of airway remodeling. (B and C) Quantitative airway morphometry showing cigarette smoke–poly(I:C) (CS+PolyI:C)–induced inflammation of the airway wall (B) and wall thickening (C), and the effects of B5 compared to control IgG2a. (D to G) Photomicrographs of mouse lungs treated with cigarette smoke–poly(I:C) and control (D and F), and cigarette smoke–poly(I:C) with B5 (E and G); H&E (D and E) and trichrome (F and G). Scale bar, 75 μm. B5 blocks cigarette smoke–poly(I:C)–induced influx of neutrophils and lymphocytes. (H to K) Total cells from the bronchoalveolar lavage (BAL) (H), macrophages (I), neutrophils (J), and lymphocytes (K). (L to O) B5 blocks the expression of cigarette smoke–poly(I:C)–induced IL-1β (L), CCL2 (M), CCL20 (N), and IL-17 (O). ELISAs were performed on whole-lung lysates for expression of IL-1β, IL-17, and CCL2 or on bronchoalveolar lavage for expression of CCL20. (P) Analysis of pSMAD3 immunostaining. (Q to S) Lung phenotyping. (Q) Mean linear intercept; L(m), estimate of airspace enlargement. (R) Airway resistance with increasing acetylcholine (ach) concentrations (log₂). (S) Concentration of acetylcholine as provocative challenge doubling baseline resistance (pc200); room air groups, n = 3; cigarette smoke–poly(I:C) groups, n = 4 to 5. *P < 0.05, **P < 0.01, ***P < 0.001, by ANOVA and Bonferroni’s post-test.