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

Effect of systemic steroids on the recruitment of MCps and appearance of eMMCs in the lung of BALB/c mice. Sensitized mice were given either HBSS (-) or prednisone (+) i.p. every other day during the challenge phase. The CD45+ lung cells were isolated and analyzed by FACS on D1 after the challenges. (a) Mean 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 MCp (green), eMMC (red) and MMC (blue) to the total number. Middle and bottom panel are bar graphs of the distinct populations that are predominant on D1, MCp (green) and eMMC (red). (c) Total number of MCs per lung in the same mice as in (b). Bar graphs represent means ± SEMs from 3 experiments with 9-12 mice/group. * p < 0.05, ** p < 0.01
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4390399&req=5

Figure 8: Effect of systemic steroids on the recruitment of MCps and appearance of eMMCs in the lung of BALB/c mice. Sensitized mice were given either HBSS (-) or prednisone (+) i.p. every other day during the challenge phase. The CD45+ lung cells were isolated and analyzed by FACS on D1 after the challenges. (a) Mean 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 MCp (green), eMMC (red) and MMC (blue) to the total number. Middle and bottom panel are bar graphs of the distinct populations that are predominant on D1, MCp (green) and eMMC (red). (c) Total number of MCs per lung in the same mice as in (b). Bar graphs represent means ± SEMs from 3 experiments with 9-12 mice/group. * p < 0.05, ** p < 0.01

Mentions: The persistence of Ag-induced lung MCs prompted an investigation of the effect of treatment with systemic steroids on the recruitment of MCps and their transition to eMMCs and on the survival of established eMMCs and MMCs using two different protocols. To examine the effect of steroid treatment on MCp recruitment, sensitized mice received prednisone or HBSS intraperitoneally (i.p.) every other day during the aerosol challenge phase with analysis 1 day after the last challenge, D1. The numbers of MCp (FcεR1loKitint) per lung along with the inflammatory response defined by numbers of leukocytes harvested from lungs are significantly decreased in challenge-phase steroid treated mice (Figure 8). The numbers of developed eMMCs are also much reduced although significance is not reached (p=0.065). The concentration of MCp and eMMC (per 106 CD45+ cells) in the lung increases with challenge of sensitized mice and this response is not reduced by treatment with steroids (Figure 8b). Thus although their numbers per lung are diminished by steroid treatment (Figure 8c), neither the MCps nor the eMMCs are selectively depleted relative to other leukocytes. In the trachea, the eMMCs (FcεR1intKitint) appearing at D1 are not reduced in number or in concentration per CD45+ leukocytes by steroid treatment (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 recruitment of MCps and appearance of eMMCs in the lung of BALB/c mice. Sensitized mice were given either HBSS (-) or prednisone (+) i.p. every other day during the challenge phase. The CD45+ lung cells were isolated and analyzed by FACS on D1 after the challenges. (a) Mean 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 MCp (green), eMMC (red) and MMC (blue) to the total number. Middle and bottom panel are bar graphs of the distinct populations that are predominant on D1, MCp (green) and eMMC (red). (c) Total number of MCs per lung in the same mice as in (b). Bar graphs represent means ± SEMs from 3 experiments with 9-12 mice/group. * p < 0.05, ** p < 0.01
© Copyright Policy
Related In: Results  -  Collection

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

Figure 8: Effect of systemic steroids on the recruitment of MCps and appearance of eMMCs in the lung of BALB/c mice. Sensitized mice were given either HBSS (-) or prednisone (+) i.p. every other day during the challenge phase. The CD45+ lung cells were isolated and analyzed by FACS on D1 after the challenges. (a) Mean 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 MCp (green), eMMC (red) and MMC (blue) to the total number. Middle and bottom panel are bar graphs of the distinct populations that are predominant on D1, MCp (green) and eMMC (red). (c) Total number of MCs per lung in the same mice as in (b). Bar graphs represent means ± SEMs from 3 experiments with 9-12 mice/group. * p < 0.05, ** p < 0.01
Mentions: The persistence of Ag-induced lung MCs prompted an investigation of the effect of treatment with systemic steroids on the recruitment of MCps and their transition to eMMCs and on the survival of established eMMCs and MMCs using two different protocols. To examine the effect of steroid treatment on MCp recruitment, sensitized mice received prednisone or HBSS intraperitoneally (i.p.) every other day during the aerosol challenge phase with analysis 1 day after the last challenge, D1. The numbers of MCp (FcεR1loKitint) per lung along with the inflammatory response defined by numbers of leukocytes harvested from lungs are significantly decreased in challenge-phase steroid treated mice (Figure 8). The numbers of developed eMMCs are also much reduced although significance is not reached (p=0.065). The concentration of MCp and eMMC (per 106 CD45+ cells) in the lung increases with challenge of sensitized mice and this response is not reduced by treatment with steroids (Figure 8b). Thus although their numbers per lung are diminished by steroid treatment (Figure 8c), neither the MCps nor the eMMCs are selectively depleted relative to other leukocytes. In the trachea, the eMMCs (FcεR1intKitint) appearing at D1 are not reduced in number or in concentration per CD45+ leukocytes by steroid treatment (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