title: Enhanced immediate inflammatory response to Streptococcus pneumoniae in the lungs of mice with pulmonary emphysema.
abstract: OBJECTIVE
  Pulmonary emphysema is associated with frequent respiratory infections but little is known about the reasons for this susceptibility to bacterial infection. We previously demonstrated an impaired inflammatory response to Streptococcus pneumoniae in an experimental emphysema mouse model at 24 h, or longer following bacterial inoculation. Toll-like receptors (TLR) have been recognized as regulators in the inflammatory response. We examined the expression of TLR on alveolar macrophages in experimental emphysema mice and evaluated the immediate inflammatory response of the emphysematous lung to streptococcal infection.
  
  
  METHODS
  Elastase was administered once into mice trachea to induce pulmonary emphysema. Three weeks later, expression of TLR-2 and TLR-4 in the BAL cells was examined by immunostaining. Following the intratracheal inoculation of Streptococcus pneumoniae, pro-inflammatory cytokine concentrations were measured in the BAL fluids of the control and emphysema mice.
  
  
  RESULTS
  The expression of TLR-2 and TLR-4 was significantly elevated in the alveolar macrophages of emphysema mice. Six hours after infection, neutrophils in the BAL fluid of emphysema mice were significantly increased, and the levels of tumour necrosis factor-alpha, IL-1beta and IL-6 were significantly elevated, compared with the control mice. At 3 h post inoculation, macrophage inflammatory protein-2 levels were significantly elevated.
  
  
  CONCLUSIONS
  The immediate inflammatory response in the emphysematous lung is significantly enhanced in response to streptococcal infection. This may be partly attributed to the increased expression of TLR in the alveolar macrophages of emphysema mice.
authors.affiliation: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Yoshikane
authors.initials: Y
authors.lastname: Tokairin
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shibata
authors.forename: Makoto
authors.initials: M
authors.lastname: Sata
authors.forename: Shuichi
authors.initials: S
authors.lastname: Abe
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takabatake
authors.forename: Akira
authors.initials: A
authors.lastname: Igarashi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Sumito
authors.initials: S
authors.lastname: Inoue
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000473:pathology; D010196:Pancreatic Elastase / Q000009:adverse effects; D011008:Pneumococcal Infections / Q000378:metabolism* / Q000382:microbiology; D011014:Pneumonia / Q000378:metabolism* / Q000382:microbiology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology; D013296:Streptococcus pneumoniae; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D010196:Pancreatic Elastase