Figure 2.

Bleomycin-induced syndecan-2 expression and decreased pulmonary fibrosis in scavenger receptor A enhancer/promoter (SREP)–human syndecan-2 (hsdc2) transgenic mice. (A) Bleomycin or saline was administered to wild-type (WT) or SREP-hsdc2 transgenic (TG) mice by aspiration, and alveolar macrophages were harvested at 0, 7, 14, or 21 days post administration. Alveolar macrophage mouse syndecan-2 mRNA levels in WT mice and human syndecan-2 mRNA levels in TG mice were assessed by quantitative real-time polymerase chain reaction (n = 10). Syndecan-2 mRNA level was up-regulated by bleomycin-induced lung injury at all time points after bleomycin administration (*P < 0.05 and **P < 0.01 compared with saline control). (B) Representative Western blot analyses using anti–syndecan-2 antibody to detect total human and mouse syndecan-2 protein in alveolar macrophages (AM) and bronchoalveolar lavage (BAL) fluid showed increased syndecan-2 levels in WT and TG mice 21 days after administration of bleomycin (BL) compared with saline (SA). (C) Alveolar macrophage numbers in TG mice were significantly increased 21 days after bleomycin-induced lung injury compared with WT mice (**P < 0.01; n = 8–12). There were no significant changes in alveolar macrophages 7 and 14 days after bleomycin administration. (D) WT mice have significantly higher hydroxyproline lung levels following exposure to bleomycin compared with saline (*P = 0.02). Hydroxyproline content in the left lung 21 days after instillation of bleomycin, and not saline, was not increased in TG mice 21 days after instillation of bleomycin compared with saline and was significantly different from bleomycin-instilled WT mice (**P = 0.0016; n = 8–12). Data are representative of three independent experiments. (E) Lung sections of WT and TG mice 21 days after bleomycin administration were stained with hematoxylin and eosin (H&E), trichrome, and collagen-1a1 antibody. Pulmonary fibrosis was decreased in TG mice compared with WT control mice (scale bar = 200 μm).