Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis
Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease with limited therapeutic options. The infiltration of monocytes and fibroblasts into the injured lungs is implicated in IPF. Enolase-1 (ENO1) is a cytosolic glycolytic enzyme which could translocate onto the cell surf...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-023-02583-3 |
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| author | Wei-Ching Huang Chi-Fen Chuang Yung-Tsang Huang I-Che Chung Mao-Lin Chen Tung-Yueh Chuang Xiu-Li Yang Yu-Yau Chou Chih-Hsin Liu Nai-Yu Chen Chun-Jen Chen Ta-Tung Yuan |
| author_facet | Wei-Ching Huang Chi-Fen Chuang Yung-Tsang Huang I-Che Chung Mao-Lin Chen Tung-Yueh Chuang Xiu-Li Yang Yu-Yau Chou Chih-Hsin Liu Nai-Yu Chen Chun-Jen Chen Ta-Tung Yuan |
| author_sort | Wei-Ching Huang |
| collection | DOAJ |
| description | Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease with limited therapeutic options. The infiltration of monocytes and fibroblasts into the injured lungs is implicated in IPF. Enolase-1 (ENO1) is a cytosolic glycolytic enzyme which could translocate onto the cell surface and act as a plasminogen receptor to facilitate cell migration via plasmin activation. Our proprietary ENO1 antibody, HL217, was screened for its specific binding to ENO1 and significant inhibition of cell migration and plasmin activation (patent: US9382331B2). Methods In this study, effects of HL217 were evaluated in vivo and in vitro for treating lung fibrosis. Results Elevated ENO1 expression was found in fibrotic lungs in human and in bleomycin-treated mice. In the mouse model, HL217 reduced bleomycin-induced lung fibrosis, inflammation, body weight loss, lung weight gain, TGF-β upregulation in bronchial alveolar lavage fluid (BALF), and collagen deposition in lung. Moreover, HL217 reduced the migration of peripheral blood mononuclear cells (PBMC) and the recruitment of myeloid cells into the lungs. In vitro, HL217 significantly reduced cell-associated plasmin activation and cytokines secretion from primary human PBMC and endothelial cells. In primary human lung fibroblasts, HL217 also reduced cell migration and collagen secretion. Conclusions These findings suggest multi-faceted roles of cell surface ENO1 and a potential therapeutic approach for pulmonary fibrosis. |
| first_indexed | 2024-03-10T17:10:10Z |
| format | Article |
| id | doaj.art-759c1be2a8654217be1fb3b6c082fdbc |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-10T17:10:10Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-759c1be2a8654217be1fb3b6c082fdbc2023-11-20T10:40:47ZengBMCRespiratory Research1465-993X2023-11-0124111510.1186/s12931-023-02583-3Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosisWei-Ching Huang0Chi-Fen Chuang1Yung-Tsang Huang2I-Che Chung3Mao-Lin Chen4Tung-Yueh Chuang5Xiu-Li Yang6Yu-Yau Chou7Chih-Hsin Liu8Nai-Yu Chen9Chun-Jen Chen10Ta-Tung Yuan11HuniLife Biotechnology IncHuniLife Biotechnology IncHuniLife Biotechnology IncHuniLife Biotechnology IncHuniLife Biotechnology IncHuniLife Biotechnology IncHuniLife Biotechnology IncHuniLife Biotechnology IncHuniLife Biotechnology IncDepartment of Biochemical Science and Technology, College of Life Science, National Taiwan UniversityDepartment of Biochemical Science and Technology, College of Life Science, National Taiwan UniversityHuniLife Biotechnology IncAbstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease with limited therapeutic options. The infiltration of monocytes and fibroblasts into the injured lungs is implicated in IPF. Enolase-1 (ENO1) is a cytosolic glycolytic enzyme which could translocate onto the cell surface and act as a plasminogen receptor to facilitate cell migration via plasmin activation. Our proprietary ENO1 antibody, HL217, was screened for its specific binding to ENO1 and significant inhibition of cell migration and plasmin activation (patent: US9382331B2). Methods In this study, effects of HL217 were evaluated in vivo and in vitro for treating lung fibrosis. Results Elevated ENO1 expression was found in fibrotic lungs in human and in bleomycin-treated mice. In the mouse model, HL217 reduced bleomycin-induced lung fibrosis, inflammation, body weight loss, lung weight gain, TGF-β upregulation in bronchial alveolar lavage fluid (BALF), and collagen deposition in lung. Moreover, HL217 reduced the migration of peripheral blood mononuclear cells (PBMC) and the recruitment of myeloid cells into the lungs. In vitro, HL217 significantly reduced cell-associated plasmin activation and cytokines secretion from primary human PBMC and endothelial cells. In primary human lung fibroblasts, HL217 also reduced cell migration and collagen secretion. Conclusions These findings suggest multi-faceted roles of cell surface ENO1 and a potential therapeutic approach for pulmonary fibrosis.https://doi.org/10.1186/s12931-023-02583-3Enolase-1AntibodyPlasminMigrationFibroblastsMonocytes |
| spellingShingle | Wei-Ching Huang Chi-Fen Chuang Yung-Tsang Huang I-Che Chung Mao-Lin Chen Tung-Yueh Chuang Xiu-Li Yang Yu-Yau Chou Chih-Hsin Liu Nai-Yu Chen Chun-Jen Chen Ta-Tung Yuan Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis Respiratory Research Enolase-1 Antibody Plasmin Migration Fibroblasts Monocytes |
| title | Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis |
| title_full | Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis |
| title_fullStr | Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis |
| title_full_unstemmed | Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis |
| title_short | Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis |
| title_sort | monoclonal enolase 1 blocking antibody ameliorates pulmonary inflammation and fibrosis |
| topic | Enolase-1 Antibody Plasmin Migration Fibroblasts Monocytes |
| url | https://doi.org/10.1186/s12931-023-02583-3 |
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