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

Bankova LG, Dwyer DF, Liu AY, Austen KF, Gurish MF - Mucosal Immunol (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Persistence of histological MMC hyperplasia in the lung and trachea. Time course showing the changes in the numbers of MMCs and CMCs in trachea and MMCs in large airways of sensitized BALB/c mice challenged up to 77 days previously or unchallenged, as assessed by histology. (a) The number of interepithelial MMCs per 3 tracheal rings. (b) The number of submucosal CMCs per 3 tracheal rings. (c) The number of interepithelial MMCs per 15 bronchovascular bundles (BVB) assessed in the large bronchi (greater than 200 μm). Each dot is a separate mouse and the bar indicates mean value from 4 experiments. *p< 0.05, **p< 0.01, ***p< 0.001.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4390399&req=5

Figure 7: Persistence of histological MMC hyperplasia in the lung and trachea. Time course showing the changes in the numbers of MMCs and CMCs in trachea and MMCs in large airways of sensitized BALB/c mice challenged up to 77 days previously or unchallenged, as assessed by histology. (a) The number of interepithelial MMCs per 3 tracheal rings. (b) The number of submucosal CMCs per 3 tracheal rings. (c) The number of interepithelial MMCs per 15 bronchovascular bundles (BVB) assessed in the large bronchi (greater than 200 μm). Each dot is a separate mouse and the bar indicates mean value from 4 experiments. *p< 0.05, **p< 0.01, ***p< 0.001.

Mentions: Because our analyses by FACS and prior studies of lung and trachea by histology28 had shown induction of MMCs by D1 but had not addressed their duration, we evaluated the time course for induction and resolution of challenge-induced MMCs in lung and trachea by histology. Intraepithelial MMCs in the trachea are significantly increased on D1 and their numbers increase further to a plateau from D7-21 consistent with the analysis by FACS (Figure 7a). Although, there is a gradual decrease in MMC numbers thereafter, the numbers at D42 and D77 are still greater than for the NC controls. The number of tracheal CMCs does not change over the 77 days (Figure 7b), consistent with previous results for D1-7.28 Histological analysis also demonstrates a distinct phenotype for tracheal MMC characterized by larger granules and smaller sized cells relative to the tracheal CMC (Supplemental Figure 1). This phenotypic difference between the major classes of MCs has been described in the mouse small intestine.10


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

Bankova LG, Dwyer DF, Liu AY, Austen KF, Gurish MF - Mucosal Immunol (2014)

Persistence of histological MMC hyperplasia in the lung and trachea. Time course showing the changes in the numbers of MMCs and CMCs in trachea and MMCs in large airways of sensitized BALB/c mice challenged up to 77 days previously or unchallenged, as assessed by histology. (a) The number of interepithelial MMCs per 3 tracheal rings. (b) The number of submucosal CMCs per 3 tracheal rings. (c) The number of interepithelial MMCs per 15 bronchovascular bundles (BVB) assessed in the large bronchi (greater than 200 μm). Each dot is a separate mouse and the bar indicates mean value from 4 experiments. *p< 0.05, **p< 0.01, ***p< 0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4390399&req=5

Figure 7: Persistence of histological MMC hyperplasia in the lung and trachea. Time course showing the changes in the numbers of MMCs and CMCs in trachea and MMCs in large airways of sensitized BALB/c mice challenged up to 77 days previously or unchallenged, as assessed by histology. (a) The number of interepithelial MMCs per 3 tracheal rings. (b) The number of submucosal CMCs per 3 tracheal rings. (c) The number of interepithelial MMCs per 15 bronchovascular bundles (BVB) assessed in the large bronchi (greater than 200 μm). Each dot is a separate mouse and the bar indicates mean value from 4 experiments. *p< 0.05, **p< 0.01, ***p< 0.001.
Mentions: Because our analyses by FACS and prior studies of lung and trachea by histology28 had shown induction of MMCs by D1 but had not addressed their duration, we evaluated the time course for induction and resolution of challenge-induced MMCs in lung and trachea by histology. Intraepithelial MMCs in the trachea are significantly increased on D1 and their numbers increase further to a plateau from D7-21 consistent with the analysis by FACS (Figure 7a). Although, there is a gradual decrease in MMC numbers thereafter, the numbers at D42 and D77 are still greater than for the NC controls. The number of tracheal CMCs does not change over the 77 days (Figure 7b), consistent with previous results for D1-7.28 Histological analysis also demonstrates a distinct phenotype for tracheal MMC characterized by larger granules and smaller sized cells relative to the tracheal CMC (Supplemental Figure 1). This phenotypic difference between the major classes of MCs has been described in the mouse small intestine.10

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

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.

No MeSH data available.


Related in: MedlinePlus