Adenovirus Vector Expressing Keratinocyte Growth Factor Using CAG Promoter Impaired Pulmonary Function of Elastase ‐induced Emphysema

Abstract Pulmonary emphysema impairs quality of life and increases mortality. Previous studies demonstrated that administration of KGF before elastase instillation prevented pulmonary emphysema in mice. We hypothesized that KGF could improve pulmonary function, and that the therapeutic administration of KGF would restore damaged lungs caused by elastase instillation in an animal model. We constructed KGF expressing adenovirus vector, which prevented bleomycin induced pulmonary fibrosis in the previous study. Adenovirus vector (1.0x109 plaque‐forming units) was administered intratracheally one week after the administration of elastase into mouse lungs. One week after the administration of KGF‐vector, exercise tolerance test and blood gas analysis was done, then lungs were harvested under deep anesthesia. KGF positive pneumocytes, and surfactant protein secretion in the airspace were indeed increased and mean linear intercept of lungs was shorter in the KGF administered animals. Unexpectedly, however, arterial blood oxygenation was deteriorated in the KGF group, and maximum running speed as an indicator of exercise tolerability was not improved with KGF in the elastase induced emphysema. Therefore, KGF‐expressing adenovirus vector impaired the pulmonary functions in the elastase‐induced emphysema. Notably, the vector lacking KGF‐expression unit did not impair them, implying that the KGF expression unit itself may cause the damage of alveolar cells. Possible involvemen...
Source: Microbiology and Immunology - Category: Microbiology Authors: Tags: Original Article Source Type: research