Journal Article

Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis

Chung, I-Che, Chuang, Chi-Fen, Chen, Nai-Yu, Chen, Mao-Lin, Liu, Chih-Hsin, Huang, Wei-Ching, Chen, Chun-Jen, Chuang, Tung-Yueh, Huang, Yung-Tsang, Chou, Yu-Yau, Yuan, Ta-Tung, Yang, Xiu-Li

2023

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Alveoli / Analysis / Animals / Antibodies / Antibodies, Monoclonal - therapeutic use / Antibody / Bacterial pneumonia / Bleomycin / Bleomycin - toxicity / Blocking antibodies / Body weight / Body weight loss / Care and treatment / Cell activation / Cell surface / Collagen / Collagen - metabolism / Diagnosis / Dosage and administration / Endothelial cells / Endothelial Cells - metabolism / Enolase-1 / Fibrinolysin - metabolism / Fibrinolysin - pharmacology / Fibrinolysin - therapeutic use / Fibroblasts / Fibroblasts - metabolism / Fibrosis / Flow cytometry / Glycolysis / Humans / Idiopathic Pulmonary Fibrosis - chemically induced / Idiopathic Pulmonary Fibrosis - drug therapy / Idiopathic Pulmonary Fibrosis - metabolism / In vivo methods and tests / Inflammation / Laboratory animals / Leukocyte migration / Leukocytes (mononuclear) / Leukocytes, Mononuclear - metabolism / Lung - metabolism / Lung diseases / Lungs / Medicine / Medicine & Public Health / Mice / Mice, Inbred C57BL / Migration / Monoclonal antibodies / Monocytes / Myeloid cells / Patient outcomes / Peripheral blood mononuclear cells / Phosphopyruvate hydratase / Phosphopyruvate Hydratase - metabolism / Phosphopyruvate Hydratase - pharmacology / Phosphopyruvate Hydratase - therapeutic use / Plasmin / Pneumology/Respiratory System / Pneumonia / Pneumonia - metabolism / Prevention / Prostate cancer / Pulmonary fibrosis / Risk factors / Thrombolytic drugs / Transforming growth factor-b / Transforming growth factors / Weight loss