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A novel single‐chain‐Fv antibody against connective tissue growth factor attenuates bleomycin‐induced pulmonary fibrosis in mice
Author(s) -
WANG XIHUA,
WU GUOQIU,
GOU LIXIA,
LIU ZHAOZHAO,
WANG XIYONG,
FAN XIAOBO,
WU LINYUAN,
LIU NAIFENG
Publication year - 2011
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2011.01938.x
Subject(s) - bleomycin , medicine , pulmonary fibrosis , connective tissue , fibrosis , antibody , pathology , cancer research , immunology , chemotherapy
Background and objective: Connective tissue growth factor (CTGF) has been identified as playing critical roles in fibrosis and is a promising therapeutic target. In a previous study, we used a phage display library to develop a humanized single‐chain variable fragment antibody (scFv) against CTGF. In the present study, the protective effect of anti‐CTGF scFv against bleomycin (BL)‐induced pulmonary fibrosis was investigated in mice. Methods: The expression of α‐smooth muscle actin in human embryonic lung fibroblast (HELF) cells was analysed by western blotting. A mouse model of pulmonary fibrosis was established by tracheal injection of BL (5 mg/kg). Mice received anti‐CTGF scFv (4 mg/kg, three times a week) by i.v. injection. The effects of anti‐CTGF scFv were evaluated by leukocyte counts in BAL fluid, hydroxyproline measurements in lung tissue and pathological examination. Results: α‐Smooth muscle actin expression was decreased in HELF cells treated with anti‐CTGF scFv. Anti‐CTGF scFv significantly reduced the numbers of inflammatory leukocytes (total and differential count) in BAL fluid, as well as the hydroxyproline content of lung tissue. The severity of alveolitis and fibrosis in the mouse model was markedly attenuated by treatment with anti‐CTGF scFv. Conclusions: Anti‐CTGF scFv may potentially be developed as a useful inhibitor of pulmonary fibrosis.