Maturation of mast cell progenitors to mucosal mast cells during allergic pulmonary inflammation in mice

Mucosal Immunol. 2015 May;8(3):596-606. doi: 10.1038/mi.2014.91. Epub 2014 Oct 8.

Abstract

In contrast to resident constitutive mast cells (CMCs), mucosal MCs (MMCs) appear in the lung and trachea of sensitized mice only following inhalation challenge. We monitored the influx and maturation of MCs by their expression of Kit, FcɛRI, β7-integrin and side scatter (SSC) by flow cytometry. Influx of MC progenitors (MCps) (FcɛRI(lo), Kit(int), β7(hi), and SSC(lo)) peaks 1 day after challenges and subsides to baseline by day 7 after challenge. The mature MMCs appear as a distinct population on day 7 and peak at day 14 with higher SSC and FcɛRI expression, but lower β7 and Kit expression. A distinct transitional population is present between 1 and 7 days after challenge. Maturation occurs more rapidly in the trachea. The resident tracheal CMCs had higher SSC, FcɛRI, and Kit and lower β7-integrin expression than the MMCs. By histology, the MMCs follow similar kinetics to the flow cytometry-identified mature MMCs and are notably persistent for >42 days. Steroid treatment reduced inflammation and MCp influx but had no effect on established MMCs. Thus, changes in SSC, FcɛRI, and Kit together with the expression of αE/α4:β7-integrins characterizes the development of induced MMCs from MCps and distinguishes them from resident CMCs in the trachea and large airways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Differentiation
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Integrin beta Chains / genetics
  • Integrin beta Chains / immunology
  • Mast Cells / immunology*
  • Mast Cells / pathology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy
  • Pneumonia / genetics
  • Pneumonia / immunology*
  • Prednisone / pharmacology
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / immunology
  • Receptors, IgE / genetics
  • Receptors, IgE / immunology
  • Respiratory Hypersensitivity / chemically induced
  • Respiratory Hypersensitivity / drug therapy
  • Respiratory Hypersensitivity / genetics
  • Respiratory Hypersensitivity / immunology*
  • Signal Transduction
  • Stem Cells / immunology*
  • Stem Cells / pathology
  • Trachea / immunology*
  • Trachea / pathology

Substances

  • Anti-Inflammatory Agents
  • Integrin beta Chains
  • Receptors, IgE
  • integrin beta7
  • Ovalbumin
  • Proto-Oncogene Proteins c-kit
  • Prednisone