title: Myeloperoxidase deficiency in mice exacerbates lung inflammation induced by nonviable Candida albicans.
abstract: OBJECTIVE
  This study aimed to evaluate the effect of myeloperoxidase (MPO) deficiency on lung inflammation induced by nonviable Candida albicans (nCA).
  
  
  METHODS
  Mice were inoculated intranasally with nCA, and accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid was analyzed by flow cytometry. The levels of macrophage inflammatory protein 2 (MIP-2), keratinocyte-derived chemokine (KC), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in the lung were measured by ELISA. Production of MIP-2 and KC from neutrophils and macrophages was quantified in vitro. MIP-2 mRNA expression in the neutrophils was analyzed by real-time reverse transcription-PCR, and the extent of phosphorylation of ERK1/2 and Syk in the neutrophils was analyzed by Western blotting.
  
  
  RESULTS
  The MPO(-/-) mice that received nCA showed more severe pneumonia than wild-type mice. Within 12 h of nCA administration, MPO(-/-) mice had significantly higher numbers of alveolar neutrophils and increased production of MIP-2 and KC relative to the responses seen in wild-type mice. Neutralization of MIP-2 and KC in vivo significantly reduced neutrophil infiltration. In vitro, production of MIP-2, but not that of KC, was enhanced in the nCA-stimulated neutrophils from MPO(-/-) mice, concomitant with up-regulation of Syk and ERK1/2. At 1 and 3 days after nCA administration, MPO(-/-) mice had significantly higher lung concentrations of TNF-α and IL-1β than wild-type mice.
  
  
  CONCLUSIONS
  Pulmonary administration of nCA produced an altered inflammatory response in MPO(-/-) mice relative to wild-type mice. Enhanced MIP-2 production by MPO(-/-) neutrophils may at least partly contribute to exacerbated inflammation in mutant mice.
authors: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa, Yokohama, 236-0027, Japan.
authors: Mizuki
authors: M
authors: Homme
authors: Nao
authors: N
authors: Tateno
authors: Noriko
authors: N
authors: Miura
authors: Naohito
authors: N
authors: Ohno
authors: Yasuaki
authors: Y
authors: Aratani
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002176:Candida albicans / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005269:Femur / Q000166:cytology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008661:Metabolism, Inborn Errors / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines
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