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Involvement of Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) in Bleomycin-Induced Pulmonary Fibrosis

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A2657 - Involvement of Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) in Bleomycin-Induced Pulmonary Fibrosis
Author Block: M. Kim1, J. Hong1, K. Kim1, Y. Lee2, J. Lee3, M. Sohn1; 1Department of Pediatrics and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea, Republic of, 2Department of Pediatrics, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea, Republic of, 3Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Korea, Republic of.
Rationale: Idiopathic pulmonary fibrosis is a chronic, progressive lung disease characterized by fibroproliferative matrix molecule accumulation, collagen deposition and apoptosis, eventually resulting in pulmonary dysfunction and death. Activated leukocyte cell-adhesion molecule (ALCAM; CD166) is a cell adhesion molecule that has been implicated in adhesive and migratory attribution including leukocyte homing and trafficking and the cancer metastasis. We investigated the involvement of ALCAM on development of bleomycin-induced pulmonary fibrosis in murine model. Methods: Bleomycin-induced pulmonary fibrosis model was established with wild type and ALCAM knockout mice. Pulmonary fibrosis was also induced in TGF- β transgenic mice that conditionally overexpress TGF-β upon doxycycline administration. Levels of ALCAM were measured in lung tissue and bronchial alveolar lavage fluid (BALF) of wild type mice and TGF- β transgenic mice. Histopathologic investigation of pulmonary fibrosis was accessed by the haematoxylin and eosin stain and ashcroft score. Masson's trichrome stain and sircol assay were performed to examine the collagen deposition. The Level of ALCAM in sputum of idiopathic pulmonary fibrosis patients and control subjects were quantified with ELISA. Result: The protein and mRNA levels of ALCAM were decreased in the BALF and lung tissue of bleomycin-treated wild type mice. Reduced ALCAM level was observed in BALF of doxycycline administered TGF-β transgenic mice relative to those of control mice. ALCAM knockout mice showed diminished lung fibrosis response compared with wild type mice upon bleomycin treatment. Sputum ALCAM level was lower in idiopathic pulmonary fibrosis patients than in control subjects Conclusion: ALCAM contributes to bleomycin-induced pulmonary fibrosis associated with TGF-β response.
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