Urease and Helicobacter spp. antigens in pulmonary granuloma

Abstract

Pulmonary sarcoidosis, a human disease of unknown cause, has no animal model. Sarcoidosis patients have serum antibodies specific for Helicobacter pylori and its surface enzyme urease. H. pylori do not survive in the high-oxygen pulmonary atmosphere, but urease may access the lung by oesophageal reflux. A model was established in rats to study gastro-oesophageal reflux of urease into the airways. Pathology in tissues from human sarcoidosis patients was compared with that in the rat model. Changes observed in the rat model included prominent peribronchial lymphocytic infiltration, which is seen occasionally in human sarcoidosis. Granulomas, pathognomonic for human sarcoidosis, occurred occasionally in the lungs of rats given urease protein intratracheally, but were widespread when urease was coupled to microbeads and administered intravenously. Biomarkers associated with human sarcoidosis (interleukin1-β and platelet-activating factor) were up-regulated acutely in the rat model. Further investigations with this model may provide significant insights into the origin and pathogenesis of pulmonary diseases in man and other species that carry gastric Helicobacter spp. and its associated enzyme.