TRAIL-Dependent Resolution of Pulmonary Fibrosis

Figure 1

Bone marrow mobilization using systemically administered clodronate liposomes increased the accumulation of Gr-1⁺ myeloid cells in the lung and is associated with reduced pulmonary fibrosis. (a) Mice either received an intraperitoneal injection of liposomes containing clodronate (Clod Lipo) or empty liposomes (Lipo) at 1 day prior to (D−1) an intrapulmonary bleomycin challenge. All mice were subsequently sacrificed at day 5 after bleomycin challenge, and lungs from D−1 Clod Lipo- or Lipo-treated mice were digested to generate a cellular suspension, and cells were stained with monoclonal antibodies directed against Gr-1, CD11b, CD11c, F4/80, CD3, CD19, γδ TCR, or NK 1.1 and analyzed by flow cytometry. (b) Mice either received an intraperitoneal injection of liposomes containing clodronate (Clod Lipo) either 1 day prior to (D−1) or at 14 days after (D+14) or empty liposomes (Lipo) one day prior to intrapulmonary bleomycin challenge. All mice were subsequently sacrificed at day 21 after bleomycin challenge and their lungs were isolated for analysis. Whole lungs were fixed, paraffin-embedded, sectioned, and Masson’s trichrome-stained to visualize ECM. Shown are representative images taken at 200x magnification. (c) Quantitative PCR analysis of procollagen 3 and fibronectin 1 in whole lung samples. (d) ELISA analysis of whole lung levels of IFN-γ, IL-4, IL-13, TGF-β, CCL22, and CCL17. Data are mean ± SEM, n = 5–10/group, compared with Lipo-alone group.

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