title: The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model.
abstract: BACKGROUND
  Intranasal inoculation of Streptococcus pneumoniae D39 serotype 2 causes fatal pneumonia in mice. The cytotoxic and inflammatory properties of pneumolysin (PLY) have been implicated in the pathogenesis of pneumococcal pneumonia.
  
  
  METHODS
  To examine the role of PLY in this experimental model we performed ELISA assays for PLY quantification. The distribution patterns of PLY and apoptosis were established by immunohistochemical detection of PLY, caspase-9 activity and TUNEL assay on tissue sections from mice lungs at various times, and the results were quantified with image analysis. Inflammatory and apoptotic cells were also quantified on lung tissue sections from antibody treated mice.
  
  
  RESULTS
  In bronchoalveolar lavages (BAL), total PLY was found at sublytic concentrations which were located in alveolar macrophages and leukocytes. The bronchoalveolar epithelium was PLY-positive, while the vascular endothelium was not PLY reactive. The pattern and extension of cellular apoptosis was similar. Anti-PLY antibody treatment decreased the lung damage and the number of apoptotic and inflammatory cells in lung tissues.
  
  
  CONCLUSIONS
  The data strongly suggest that in vivo lung injury could be due to the pro-apoptotic and pro-inflammatory activity of PLY, rather than its cytotoxic activity. PLY at sublytic concentrations induces lethal inflammation in lung tissues and is involved in host cell apoptosis, whose effects are important to pathogen survival.
authors.affiliation: Area de Microbiología, Departamento de Biología Funcional, Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, Oviedo, Asturias, Spain. margarciasuarez@yahoo.es
authors.forename: María Del Mar
authors.initials: Mdel M
authors.lastname: García-Suárez
authors.forename: Noelia
authors.initials: N
authors.lastname: Flórez
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.forename: Fernando
authors.initials: F
authors.lastname: Vázquez
authors.forename: Roberto
authors.initials: R
authors.lastname: Villaverde
authors.forename: Kevin
authors.initials: K
authors.lastname: Fabrizio
authors.forename: Liise-Anne
authors.initials: LA
authors.lastname: Pirofski
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Méndez
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology*; D013301:Streptolysins / Q000276:immunology*; D015996:Survival Rate
chemical_list: D001426:Bacterial Proteins; D007155:Immunologic Factors; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae