Mast cells express IL-13Rα1: IL-13 promotes human lung mast cell proliferation and FcɛRI expression

Changes in the density and distribution of pulmonary mast cells were determined in six mammalian species exposed to hypobaric hypoxia (PB = 435 Torr) for 19–48 days. Control animals were studied at 1,600 m (PB = 635 Torr). Total lung mast cell hyperplasia was observed only in calves exposed to high altitude. Pigs, rats, and sheep exhibited small, but insignificant, increases in mast cell density. Perivascular mast cell proliferation adjacent to vessels of 30–500 mum in diameter was seen in both calves and pigs. Bronchial, alveolar septal, and systemic tissue (tongue) mast cell hyperplasia was not observed in any of the species. Three indices of pulmonary hypertension (right ventricular hypertrophy, medial thickness of pulmonary arteries, and pulmonary arterial pressure) correlated with perivascular mast cell density. The findings indicate that perivascular mast cell proliferation may relate more to the morphological pulmonary vascular changes and to pulmonary hypertension than to hypoxia, leading to the speculation that mast cells increase in number in response to the hypertension, rather than to mediate and maintain the hypertension.

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Immunoprofiling Reveals Novel Mast Cell Receptors and the Continuous Nature of Human Lung Mast Cell Heterogeneity

Frontiers in Immunology ◽

10.3389/fimmu.2021.804812 ◽

2022 ◽

Vol 12 ◽

Author(s):

Elin Rönnberg ◽

Daryl Zhong Hao Boey ◽

Avinash Ravindran ◽

Jesper Säfholm ◽

Ann-Charlotte Orre ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cell Surface ◽

Human Lung ◽

Surface Markers ◽

Cell Surface Markers ◽

Cell Heterogeneity ◽

Cell Subpopulations ◽

Lung Mast Cell ◽

Mast Cell Heterogeneity

BackgroundImmunohistochemical analysis of granule-associated proteases has revealed that human lung mast cells constitute a heterogeneous population of cells, with distinct subpopulations identified. However, a systematic and comprehensive analysis of cell-surface markers to study human lung mast cell heterogeneity has yet to be performed.MethodsHuman lung mast cells were obtained from lung lobectomies, and the expression of 332 cell-surface markers was analyzed using flow cytometry and the LEGENDScreen™ kit. Markers that exhibited high variance were selected for additional analyses to reveal whether they were correlated and whether discrete mast cell subpopulations were discernable.ResultsWe identified the expression of 102 surface markers on human lung mast cells, 23 previously not described on mast cells, of which several showed high continuous variation in their expression. Six of these markers were correlated: SUSD2, CD49a, CD326, CD34, CD66 and HLA-DR. The expression of these markers was also correlated with the size and granularity of mast cells. However, no marker produced an expression profile consistent with a bi- or multimodal distribution.ConclusionsLEGENDScreen analysis identified more than 100 cell-surface markers on mast cells, including 23 that, to the best of our knowledge, have not been previously described on human mast cells. The comprehensive expression profiling of the 332 surface markers did not identify distinct mast cell subpopulations. Instead, we demonstrate the continuous nature of human lung mast cell heterogeneity.

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Immunoprofiling reveals novel mast cell receptors and the continuous nature of human lung mast cell heterogeneity

10.22541/au.161696545.56545800/v1 ◽

2021 ◽

Author(s):

Elin Rönnberg ◽

Daryl Boey Zhong Hao ◽

Avinash Ravindran ◽

Jesper Säfholm ◽

Ann-Charlotte Orre ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cell Surface ◽

Human Lung ◽

Surface Markers ◽

Cell Surface Markers ◽

Cell Heterogeneity ◽

Cell Subpopulations ◽

Lung Mast Cell ◽

Mast Cell Heterogeneity

Background: Immunohistochemical analysis of granule-associated proteases has revealed that human lung mast cells constitute a heterogeneous population of cells, with distinct subpopulations identified. However, a systematic and comprehensive analysis of cell-surface markers to study human lung mast cell heterogeneity has yet to be performed. Methods: Human lung mast cells were obtained from lung lobectomies, and the expression of 332 cell-surface markers was analyzed using flow cytometry and the LEGENDScreen kit. Markers that exhibited high variance were selected for additional analyses to reveal whether they were correlated and whether discrete mast cell subpopulations were discernable. Results: We identified the expression of 102 surface markers on human lung mast cells. Several markers showed high continuous variation in expression within the mast cell population. Six of these markers were correlated: SUSD2, CD49a, CD326, CD34, CD66 and HLA-DR. The expression of these markers was also correlated with the size and granularity of mast cells. However, no marker produced an expression profile consistent with a bi- or multimodal distribution. Conclusions: LEGENDScreen analysis identified more than 100 cell-surface markers on mast cells, including 23 that, to the best of our knowledge, have not been previously described on human mast cells. Several of the newly described markers are known to be involved in sensing the microenvironment, and their identification can shed new light on mast cell functions. The exhaustive expression profiling of the 332 surface markers failed to detect distinct mast cell subpopulations. Instead, we demonstrate the continuous nature of human lung mast cell heterogeneity.

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Induction of Human Lung Mast Cell Apoptosis by Granule Permeabilization: A Novel Approach for Targeting Mast Cells

Frontiers in Immunology ◽

10.3389/fimmu.2017.01645 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 3

Author(s):

Aida Paivandy ◽

Martin Sandelin ◽

Helena Igelström ◽

Per Landelius ◽

Christer Janson ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cell Apoptosis ◽

Human Lung ◽

Novel Approach ◽

Lung Mast Cell

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Differences in the behavior of cytoplasmic granules and lipid bodies during human lung mast cell degranulation.

The Journal of Cell Biology ◽

10.1083/jcb.99.5.1678 ◽

1984 ◽

Vol 99 (5) ◽

pp. 1678-1687 ◽

Cited By ~ 50

Author(s):

A M Dvorak ◽

I Hammel ◽

E S Schulman ◽

S P Peters ◽

D W MacGlashan ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cell Activation ◽

Human Lung ◽

Specific Antigen ◽

Mast Cell Degranulation ◽

Mast Cell Activation ◽

Lipid Bodies ◽

Cytoplasmic Granules ◽

Lung Mast Cell

We used a morphometric and autoradiographic approach to analyze changes in specific cytoplasmic granules and cytoplasmic lipid bodies associated with human lung mast cell degranulation. Mast cells were dissociated from lung tissue by enzymatic digestion and were then enriched to purities of up to 99% by countercurrent centrifugation elutriation and recovery from columns containing specific antigen bound to Sepharose 6 MB. Degranulation was induced by goat anti-IgE. At various intervals after stimulation, parallel aliquots of cells were recovered for determination of histamine release or were fixed for transmission electron microscopy. We found that lipid bodies, electron-dense structures that lack unit membranes, were present in both control and stimulated mast cells. Autoradiographic analysis showed that lipid bodies represented the major repository of 3H-label derived from [3H]arachidonic acid taken up from the external milieu. By contrast, the specific cytoplasmic granules contained no detectable 3H-label. In addition, lipid bodies occurred in intimate association with degranulation channels during mast cell activation, but the total volume of lipid bodies did not change during the 20 min after stimulation with anti-IgE. This result stands in striking contrast to the behavior of specific cytoplasmic granules, the great majority of which (77% according to aggregate volume) exhibited ultrastructural alterations during the first 20 min of mast cell activation. These observations establish that mast cell cytoplasmic granules and cytoplasmic lipid bodies are distinct organelles that differ in ultrastructure, biochemistry, and behavior during mast cell activation.

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Immunoprofiling reveals novel mast cell receptors and a continuous nature of human lung mast cell heterogeneity

10.1101/2021.03.12.435093 ◽

2021 ◽

Author(s):

Elin Rönnberg ◽

Daryl Zhong Hao Boey ◽

Avinash Ravindran ◽

Jesper Säfholm ◽

Ann-Charlotte Orre ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cell Surface ◽

Human Lung ◽

Surface Markers ◽

Cell Surface Markers ◽

Cell Heterogeneity ◽

Cell Subpopulations ◽

Lung Mast Cell ◽

Mast Cell Heterogeneity

AbstractBackgroundImmunohistochemical analysis of granule-associated proteases have revealed that human lungs mast cells constitute a heterogeneous population of cells, with distinct subpopulations identified. However, a systematic and comprehensive analysis of cell surface markers to study human lung mast cell heterogeneity is yet to be performed.MethodsHuman lung mast cells were obtained from lung lobectomies and the expression of 332 cell surface markers were analyzed using flow cytometry and the LEGENDScreen™ kit. Markers that exhibited a high variance were selected for additional analyses to reveal whether they correlated and if discrete mast cell subpopulations were discernable.ResultsWe identified expression of 102 surface markers on human lung mast cells. Several markers showed a high continuous variation of expression within the mast cell population. Six of these markers correlated: SUSD2, CD49a, CD326, CD34, CD66 and HLA-DR. The expression of these markers also correlated to the size and granularity of the mast cells. However, no marker produced an expression profile consistent with a bi- or multimodal distribution.ConclusionsLEGENDScreen analysis identified more than 100 cell surface markers on mast cells, out of which 23 have to our knowledge not previously described on human mast cells. Several of the newly described markers are known to be involved in sensing the microenvironment, and their identification can shed new light on mast cell functions. The exhaustive expression profiling of the 332 surface markers failed to detect distinct mast cell subpopulations. Instead, we demonstrate a continuous nature of human lung mast cell heterogeneity.

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Mast Cell Heterogeneity in Human Lung Tissue

Clinical Science ◽

10.1042/cs0770297 ◽

1989 ◽

Vol 77 (3) ◽

pp. 297-304 ◽

Cited By ~ 10

Author(s):

F. J. Van Overveld ◽

L. A. M. J. Houben ◽

F. E. M. Schmitz du Moulin ◽

P. L. B. Bruijnzeel ◽

J. A. M. Raaijmakers ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Alcian Blue ◽

Lung Tissue ◽

Human Lung ◽

Immunoglobulin E ◽

Prostaglandin D2 ◽

Leukotriene C4 ◽

Human Lung Tissue ◽

No Release

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue. 2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells. 3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type. 4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell. 5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells. 6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine. 7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with antiimmunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4. 8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with antiimmunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.

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