Platelet-derived growth factor is involved in the augmentation of airway responsiveness through remodeling of airways in diesel exhaust particulate-treated mice

Abstract

Background: Thickening of the region adjacent to the basement membrane is a key component of the remodeling of the asthmatic airway and is caused by collagen deposition in the region. Objective: We sought to clarify the role of platelet-derived growth factor (PDGF), a competence factor of fibroblast, in the enhanced airway responsiveness and remodeling in a murine model. Methods: Diesel exhaust particulates (DEPs) were administered intranasally every other day for 2 weeks with or without anti-PDGF-β neutralizing antibody or goat IgG. Pulmonary function was then analyzed by using whole-body plethysmography before and after acetylcholine inhalation. Results: Anti-PDGF-β neutralizing antibody significantly inhibited both the elevation of airway resistance elicited by 1.25 and 2.5 mg/mL acetylcholine and the increase in the airway wall thickening induced by DEPs. In addition, bronchoalveolar lavage fluid cell analysis revealed that anti-PDGF-β neutralizing antibody did not affect cellular infiltration at the airways. Conclusion: PDGF plays an important role in the process of remodeling brought about by DEP exposure in mice.