title: Severe neutrophil-mediated lung inflammation in myeloperoxidase-deficient mice exposed to zymosan.
abstract: OBJECTIVE
  This study examines the role of myeloperoxidase (MPO), a major constituent of neutrophils that generates hypochlorous acid, in neutrophil recruitment into the zymosan-exposed lung of mice.
  
  
  METHODS
  Mice were inoculated intranasally with zymosan. The accumulation of neutrophils and other inflammatory cells within the lung was analyzed by flow cytometry. Macrophage inflammatory protein 2 (MIP-2) expression in the lung was quantified, and the contribution of this chemokine to neutrophil accumulation was examined by intranasal administration of MIP-2 antibody. The cellular sources of MIP-2 were identified, and the production of this chemokine from macrophages and neutrophils was quantified in vitro.
  
  
  RESULTS
  Zymosan exposure led to greater neutrophil infiltration into the lungs of MPO(-/-) mice relative to wild-type mice. This was associated with higher MIP-2 levels in the mutant mice. Neutralization of MIP-2 in vivo significantly reduced neutrophil infiltration. Neutrophils from MPO(-/-) mice produced more MIP-2, and the production was reduced when MPO was added exogenously.
  
  
  CONCLUSIONS
  MPO deficiency results in severe lung inflammation in mice exposed to zymosan. Relatively high MIP-2 levels likely contribute to the strong inflammatory response in these animals.
authors: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa, Yokohama 236-0027, Japan.
authors: Kazuhiro
authors: K
authors: Takeuchi
authors: Yu
authors: Y
authors: Umeki
authors: Noriko
authors: N
authors: Matsumoto
authors: Kei
authors: K
authors: Yamamoto
authors: Mina
authors: M
authors: Yoshida
authors: Kazuo
authors: K
authors: Suzuki
authors: Yasuaki
authors: Y
authors: Aratani
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D054426:Chemokine CXCL2 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D009195:Peroxidase / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D015054:Zymosan
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D015054:Zymosan; D009195:Peroxidase