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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

Effect of systemic steroids on the post challenge presence of induced MCs in the lung of BALB/c mice. Sensitized and challenged mice were given 4 doses of HBSS (-) or prednisone (+) i.p. every other day for 7 days after the challenge phase starting on D1 post challenge. The lung cells were isolated and analyzed by FACS on D7 after the challenges. (a) Mean cell counts of leukocytes from the lung preparations. (b) Concentration of FcεR1+Kit+MCs/106 CD45+ cells in the lung determined by FACS. Top panel; stacked bars represent the concentration of all MCs and show the relative contribution of the MCp (green), eMMC (red) and MMC (blue) to the total number. Middle and bottom panels are bar graphs of the distinct populations that are predominant on D7 – eMMC (red) and MMC (blue). (c) Total number of MCs per lung in the same mice as in (b). Bar graphs represent means ± SEMs from 3 experiments with 9 mice/group. * p < 0.05.
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Figure 9: Effect of systemic steroids on the post challenge presence of induced MCs in the lung of BALB/c mice. Sensitized and challenged mice were given 4 doses of HBSS (-) or prednisone (+) i.p. every other day for 7 days after the challenge phase starting on D1 post challenge. The lung cells were isolated and analyzed by FACS on D7 after the challenges. (a) Mean cell counts of leukocytes from the lung preparations. (b) Concentration of FcεR1+Kit+MCs/106 CD45+ cells in the lung determined by FACS. Top panel; stacked bars represent the concentration of all MCs and show the relative contribution of the MCp (green), eMMC (red) and MMC (blue) to the total number. Middle and bottom panels are bar graphs of the distinct populations that are predominant on D7 – eMMC (red) and MMC (blue). (c) Total number of MCs per lung in the same mice as in (b). Bar graphs represent means ± SEMs from 3 experiments with 9 mice/group. * p < 0.05.

Mentions: To examine the effect of steroid treatment on established eMMCs and MMCs, sensitized and challenged mice were treated with prednisone beginning 1 day after the last challenge, D1, and every other day until analysis on D7. By D7 the inflammatory infiltrate is essentially dissipated and the additional reduction in the lung leukocytes with steroid administration is not significant (Figure 9a). Neither the numbers per lung nor the concentration (per 106 CD45+ cells) of eMMCs alone, or plus MMCs, are reduced by steroid treatment as compared to the HBSS treated mice (Figure 9b and c). Similarly, in the trachea the post challenge administration of corticosteroids has no effect on the numbers or concentration of eMMCs and MMCs (data not shown)


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)

Effect of systemic steroids on the post challenge presence of induced MCs in the lung of BALB/c mice. Sensitized and challenged mice were given 4 doses of HBSS (-) or prednisone (+) i.p. every other day for 7 days after the challenge phase starting on D1 post challenge. The lung cells were isolated and analyzed by FACS on D7 after the challenges. (a) Mean cell counts of leukocytes from the lung preparations. (b) Concentration of FcεR1+Kit+MCs/106 CD45+ cells in the lung determined by FACS. Top panel; stacked bars represent the concentration of all MCs and show the relative contribution of the MCp (green), eMMC (red) and MMC (blue) to the total number. Middle and bottom panels are bar graphs of the distinct populations that are predominant on D7 – eMMC (red) and MMC (blue). (c) Total number of MCs per lung in the same mice as in (b). Bar graphs represent means ± SEMs from 3 experiments with 9 mice/group. * p < 0.05.
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Related In: Results  -  Collection

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Figure 9: Effect of systemic steroids on the post challenge presence of induced MCs in the lung of BALB/c mice. Sensitized and challenged mice were given 4 doses of HBSS (-) or prednisone (+) i.p. every other day for 7 days after the challenge phase starting on D1 post challenge. The lung cells were isolated and analyzed by FACS on D7 after the challenges. (a) Mean cell counts of leukocytes from the lung preparations. (b) Concentration of FcεR1+Kit+MCs/106 CD45+ cells in the lung determined by FACS. Top panel; stacked bars represent the concentration of all MCs and show the relative contribution of the MCp (green), eMMC (red) and MMC (blue) to the total number. Middle and bottom panels are bar graphs of the distinct populations that are predominant on D7 – eMMC (red) and MMC (blue). (c) Total number of MCs per lung in the same mice as in (b). Bar graphs represent means ± SEMs from 3 experiments with 9 mice/group. * p < 0.05.
Mentions: To examine the effect of steroid treatment on established eMMCs and MMCs, sensitized and challenged mice were treated with prednisone beginning 1 day after the last challenge, D1, and every other day until analysis on D7. By D7 the inflammatory infiltrate is essentially dissipated and the additional reduction in the lung leukocytes with steroid administration is not significant (Figure 9a). Neither the numbers per lung nor the concentration (per 106 CD45+ cells) of eMMCs alone, or plus MMCs, are reduced by steroid treatment as compared to the HBSS treated mice (Figure 9b and c). Similarly, in the trachea the post challenge administration of corticosteroids has no effect on the numbers or concentration of eMMCs and MMCs (data not shown)

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