The naive airway hyperresponsiveness of the A/J mouse is Kit-mediated

Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12787-92. doi: 10.1073/pnas.1106582108. Epub 2011 Jul 18.

Abstract

There is a wide variation among humans and mice in airway hyperresponsiveness (AHR) in the absence of allergen sensitization, i.e., naïve AHR. Because mast cell (MC) activation is thought to mediate AHR in atopic asthmatic subjects, we asked whether MCs mediate naïve AHR in A/J mice. We generated an A/J congenic strain lacking c-Kit by introgression of the Wv mutation, which resulted in the elimination of MCs and the abrogation of naïve AHR. Imatinib, which disrupts Kit signaling, also abrogated AHR in A/J mice. Remarkably, introduction of the Vga9 Mitf mutation into the A/J background resulted in the ablation of MCs but did not ameliorate AHR. These results indicate that c-Kit is required for development of AHR in an MC-independent fashion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Benzamides
  • Bronchial Hyperreactivity / genetics*
  • Bronchial Hyperreactivity / immunology
  • Cell Count
  • Cells, Cultured
  • Female
  • Imatinib Mesylate
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mast Cells / metabolism*
  • Mast Cells / pathology
  • Methacholine Chloride / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Pedigree
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrimidines / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology
  • Trachea / drug effects
  • Trachea / metabolism
  • Trachea / pathology

Substances

  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Methacholine Chloride
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit