Role for macrophage migration inhibitory factor in asthma

DOI Web Site 被引用文献3件
  • Y. Mizue
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • S. Ghani
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • L. Leng
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • C. McDonald
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • P. Kong
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • J. Baugh
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • S. J. Lane
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • J. Craft
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • J. Nishihira
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • S. C. Donnelly
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • Z. Zhu
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan
  • R. Bucala
    Yale University School of Medicine, New Haven, CT 06520-8031; Sapporo Immunodiagnostics, Sapporo 001-0922, Japan; Conway Institute of Biomolecular and Biomedical Research, University College, and Tallaght Hospital, Dublin 4, Ireland; and Department of Molecular Biochemistry, Hokkaido University, Sapporo 060, Japan

抄録

<jats:p> Macrophage migration inhibitory factor (MIF) is an immunologic regulator that is expressed in inflammatory and autoimmune disorders. We investigated MIF's role in asthma using genetic approaches in a mouse model and in a cohort of asthma patients. Mice genetically deficient in MIF that were primed and aerosol-challenged with ovalbumin showed less pulmonary inflammation and lower airway hyperresponsiveness than genetically matched, wild-type controls. MIF deficiency also resulted in lower titers of specific IgE, IgG <jats:sub>1</jats:sub> , and IgG <jats:sub>2a</jats:sub> , and decreased pulmonary, T <jats:sub>H</jats:sub> 2 cytokine levels. IL-5 concentrations were lower and corresponded to decreased eosinophil numbers in bronchoalveolar lavage fluid. T cell studies also showed a lower level of antigen-specific responses in MIF-KO versus wild-type mice. In an analysis of 151 white patients with mild, moderate, or severe asthma (Global Initiative for Asthma criteria), a significant association was found between mild asthma and the low-expression, 5-CATT <jats:italic>MIF</jats:italic> allele. Pharmacologic inhibition of MIF may be beneficial and could be guided by the <jats:italic>MIF</jats:italic> genotype of affected individuals. </jats:p>

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