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PMID: 16186482 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Role for macrophage migration inhibitory factor in asthma.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 40 ·2005-10-04 ·Pages 14410-5

Mizue Y, Ghani S, Leng L, McDonald C, Kong P, Baugh J, Lane SJ, Craft J, Nishihira J, Donnelly SC, Zhu Z, Bucala R

Abstract

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(1), and IgG(2a), and decreased pulmonary, T(H)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 MIF allele. Pharmacologic inhibition of MIF may be beneficial and could be guided by the MIF genotype of affected individuals.

MeSH Terms
Adult Animals Asthma/immunology,metabolism Base Sequence Bronchoalveolar Lavage Cell Proliferation Cells, Cultured Cytokines/metabolism Enzyme-Linked Immunosorbent Assay Flow Cytometry Gene Components Genotype Humans Interleukin-5/metabolism Intramolecular Oxidoreductases Macrophage Migration-Inhibitory Factors/genetics,metabolism Mice Mice, Inbred BALB C Mice, Knockout Ovalbumin Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Helper-Inducer/metabolism
Chemicals
Cytokines Interleukin-5 Macrophage Migration-Inhibitory Factors Ovalbumin Intramolecular Oxidoreductases Mif protein, mouse
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Mizue Y
Yale University School of Medicine, New Haven, CT 06520-8031, USA.
Ghani S
Leng L
McDonald C
Kong P
Baugh J
Lane S J
Craft J
Nishihira J
Donnelly S C
Zhu Z
Bucala R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0507189102
Published
2005-10-04
Epub
2005-00-26
Pages
14410-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1242335
Subset
IM
Grants
NIAMS NIH HHS · R01 AR049610 · United States
NIAMS NIH HHS · R01 AR050498 · United States
NIAMS NIH HHS · 1R01-AR050498 · United States
NIAMS NIH HHS · 1R01-AR49610 · United States
External Links
PubMed source DOI: 10.1073/pnas.0507189102 PMC Full Text View journal details
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