TY - JOUR T1 - Surface enolase-1 mediated cell migration and lung fibrosis in bleomycin-induced mice JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.PA3281 VL - 58 IS - suppl 65 SP - PA3281 AU - Wei-Ching Huang AU - Chi-Fen Chuang AU - I-Che Chung AU - Yung-Tsang Huang AU - Mao-Lin Chen AU - Ta-Tung Yuan Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/PA3281.abstract N2 - Background: Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized with progressive stiffening and scarring of the lungs. Treatment options are still in urgent needs. Upon inflammation, enolase-1 (ENO1) translocated on the cell surface to act as plasminogen receptor facilitating cell migration via plasmin activation. HuL217 is a humanized ENO1 monoclonal antibody (mAb) designed for the blockage of ENO1-mediated cell migration. We hypothesized HuL217 could block the infiltration of monocytes and migration of fibroblasts into the injured lungs to cause damage, which are implicated in the pathogenesis of IPF.Aim: To assess the effect of ENO1 mAb on experimental lung fibrosis in vivo.Methods: Lung fibrosis was induced by a single intratracheal dosing of bleomycin (3 mg/kg) in C57BL/6J mice. One day after bleomycin challenge, HuL217 (10 mg/kg) was given intravenously with a 6-day interval. Animals were monitored for body weight and lung tissues were prepared for pathological evaluation and collagen measurement by using Ashcroft scoring and Sircol assay. BALF (bronchoalveolar lavage fluid) was measured for the amounts of TGF-β and monocytes. The action mechanisms of HuL217 were investigated ex vivo using isolated primary mouse lung fibroblasts.Results: In bleomycin mice, HuL217 significantly attenuated body weight loss and lung weight gain as well as the fibrosis lesion and collagen deposition in lungs. The elevated amount of TGF-β and monocytes were also reduced in BALF. HuL217 could significantly reduce cell migration and secretion of collagen and TGF-β in primary mouse lung myofibroblasts.Measurements and Main Results: Bleomycin-induced lung fibrosis in mice could be ameliorated by ENO1 mAb.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3281.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -