title: Effects of imatinib mesylate on pulmonary allergic vasculitis in a murine model.
abstract: OBJECTIVE
  Imatinib mesylate (IM) is a potent and specific tyrosine inhibitor and has been reported to inhibit mesenchymal cell proliferation in pulmonary fibrosis. In the present study, we examine the effects of IM on vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration.
  
  
  METHODS
  C57BL/6 mice were sensitized with ovalbumin (OVA) and alum. The positive controls were exposed to aerosolized OVA daily for 7 days. IM treated mice with exposure to OVA were administered IM in parallel with daily exposure to aerosolized OVA for 7 days. On the 7th day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for pathological analysis. Cell differentials were determined and the concentrations of cytokines in the BAL fluid (BALF) were measured. Semi-quantitative analysis of pathological changes in the pulmonary arteries was evaluated according to the criteria of severity of vasculitis. Immunohistochemistry for Ki-67 to detect proliferating cells was performed.
  
  
  RESULTS
  The number of eosinophils in BALF was reduced significantly in the IM-treated group compared to the positive control. There was no significant difference in the concentrations of interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, tumor growth factor (TGF)-β or platelet-derived growth factor in the BAL fluid between the positive control and the IM-treated group. The pathological scores of vasculitis and the ratio of Ki-67-positive intra-luminal cells were reduced significantly in the IM-treated group compared to the control group after OVA exposure.
  
  
  CONCLUSIONS
  IM-suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration.
authors.affiliation: Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Suzuki
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Sasaki
authors.forename: Yu
authors.initials: Y
authors.lastname: Utsumi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nagashima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamashita
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Sawai
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid; D049109:Cell Proliferation / Q000187:drug effects; D015897:Comorbidity; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D005260:Female; D000068877:Imatinib Mesylate; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000188:drug therapy* / Q000453:epidemiology*; D014657:Vasculitis / Q000188:drug therapy* / Q000453:epidemiology* / Q000378:metabolism
chemical_list: D001549:Benzamides; D016207:Cytokines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D010047:Ovalbumin
keywords: disease aetiology and pathogenesis - Human; drug treatment; vasculitides