title: Comparative proteomic analysis of lung tissue from guinea pigs with leptospiral pulmonary haemorrhage syndrome (LPHS) reveals a decrease in abundance of host proteins involved in cytoskeletal and cellular organization.
abstract: Leptospiral pulmonary haemorrhage syndrome (LPHS) is a particularly severe form of leptospirosis. LPHS is increasingly recognized in both humans and animals and is characterized by rapidly progressive intra-alveolar haemorrhage leading to high mortality. The pathogenic mechanisms of LPHS are poorly understood which hampers the application of effective treatment regimes. In this study a 2-D guinea pig proteome lung map was created and used to investigate the pathogenic mechanisms of LPHS. Comparison of lung proteomes from infected and non-infected guinea pigs via differential in-gel electrophoresis revealed highly significant differences in abundance of proteins contained in 130 spots. Acute phase proteins were the largest functional group amongst proteins with increased abundance in LPHS lung tissue, and likely reflect a local and/or systemic host response to infection. The observed decrease in abundance of proteins involved in cytoskeletal and cellular organization in LPHS lung tissue further suggests that infection with pathogenic Leptospira induces changes in the abundance of host proteins involved in cellular architecture and adhesion contributing to the dramatically increased alveolar septal wall permeability seen in LPHS.
  
  
  CONCLUSIONS
  The recent completion of the complete genome sequence of the guinea pig (Cavia porcellus) provides innovative opportunities to apply proteomic technologies to an important animal model of disease. In this study, the comparative proteomic analysis of lung tissue from experimentally infected guinea pigs with leptospiral pulmonary haemorrhage syndrome (LPHS) revealed a decrease in abundance of proteins involved in cellular architecture and adhesion, suggesting that loss or down-regulation of cytoskeletal and adhesion molecules plays an important role in the pathogenesis of LPHS. A publically available guinea pig lung proteome map was constructed to facilitate future pulmonary proteomics in this species.
authors.affiliation: University College Dublin, School of Veterinary Medicine, Belfield, Dublin 4, Ireland; Vetsuisse Faculty University of Bern, Länggassstrasse 128, 3012 Bern, Switzerland. Electronic address: simone.schuller@vetsuisse.unibe.ch.
authors.forename: Simone
authors.initials: S
authors.lastname: Schuller
authors.affiliation: Luxembourg Institute of Science and Technology, Environmental Research and Innovation" (ERIN) department, 41, rue du Brill, 4422 Belvaux, Luxembourg.
authors.forename: Kjell
authors.initials: K
authors.lastname: Sergeant
authors.affiliation: Luxembourg Institute of Science and Technology, Environmental Research and Innovation" (ERIN) department, 41, rue du Brill, 4422 Belvaux, Luxembourg.
authors.forename: Jenny
authors.initials: J
authors.lastname: Renaut
authors.affiliation: University College Dublin, School of Veterinary Medicine, Belfield, Dublin 4, Ireland; Conway Institute for Biomolecular & Biomedical Research, Belfield, Dublin 4, Ireland; Ross University School of Veterinary Medicine, St Kitts and Nevis, West Indies.
authors.forename: John J
authors.initials: JJ
authors.lastname: Callanan
authors.affiliation: Conway Institute for Biomolecular & Biomedical Research, Belfield, Dublin 4, Ireland.
authors.forename: Caitriona
authors.initials: C
authors.lastname: Scaife
authors.affiliation: University College Dublin, School of Veterinary Medicine, Belfield, Dublin 4, Ireland; Conway Institute for Biomolecular & Biomedical Research, Belfield, Dublin 4, Ireland; Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, Department of Agriculture, Ames, IA 50010, USA.
authors.forename: Jarlath E
authors.initials: JE
authors.lastname: Nally
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D006470:Hemorrhage / Q000378:metabolism* / Q000473:pathology; D007919:Leptospira / Q000378:metabolism*; D007922:Leptospirosis / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D013577:Syndrome
chemical_list: D020543:Proteome
keywords: DIGE; Guinea pig; Leptospiral pulmonary haemorrhage syndrome; Leptospirosis; Lung proteome map