Histamine receptor H4 regulates mast cell degranulation and IgE induced FcεRI upregulation in murine bone marrow-derived mast cells

Mast cells are found in the heart and contribute to reperfusion injury following myocardial ischemia. Since the activation of A2Aadenosine receptors (A2AARs) inhibits reperfusion injury, we hypothesized that ATL146e (a selective A2AAR agonist) might protect hearts in part by reducing cardiac mast cell degranulation. Hearts were isolated from five groups of congenic mice: A2AAR+/+mice, A2AAR−/−mice, mast cell-deficient (KitW-sh/W-sh) mice, and chimeric mice prepared by transplanting bone marrow from A2AAR−/−or A2AAR+/+mice to radiation-ablated A2AAR+/+mice. Six weeks after bone marrow transplantation, cardiac mast cells were repopulated with >90% donor cells. In isolated, perfused hearts subjected to ischemia-reperfusion injury, ATL146e or CGS-21680 (100 nmol/l) decreased infarct size (IS; percent area at risk) from 38 ± 2% to 24 ± 2% and 22 ± 2% in ATL146e- and CGS-21680-treated hearts, respectively ( P < 0.05) and significantly reduced mast cell degranulation, measured as tryptase release into reperfusion buffer. These changes were absent in A2AAR−/−hearts and in hearts from chimeric mice with A2AAR−/−bone marrow. Vehicle-treated KitW-sh/W-shmice had lower IS (11 ± 3%) than WT mice, and ATL146e had no significant protective effect (16 ± 3%). These data suggest that in ex vivo, buffer-perfused hearts, mast cell degranulation contributes to ischemia-reperfusion injury. In addition, our data suggest that A2AAR activation is cardioprotective in the isolated heart, at least in part by attenuating resident mast cell degranulation.

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BODIPY®FL histamine as a new modality for quantitative detection of histamine receptor upregulation upon IgE sensitization in murine bone marrow-derived mast cells

Cytometry Part A ◽

10.1002/cyto.a.22566 ◽

2014 ◽

Vol 87 (1) ◽

pp. 23-31 ◽

Cited By ~ 4

Author(s):

Arash Mirzahosseini ◽

Marianna Kovács ◽

Károly Kánai ◽

Péter Csutora ◽

Balázs Dalmadi

Keyword(s):

Bone Marrow ◽

Mast Cells ◽

Histamine Receptor ◽

Quantitative Detection ◽

Murine Bone Marrow ◽

Receptor Upregulation

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Dynamics of Plasma and Granule Membrane in Murine Bone Marrow-Derived Mast Cells after Re-stimulation

The Open Allergy Journal ◽

10.2174/1874838401508010014 ◽

2015 ◽

Vol 8 (1) ◽

pp. 14-22

Author(s):

Masahiro Kaneko ◽

Arisa Yamada

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Plasma Membrane ◽

Mast Cells ◽

Morphological Changes ◽

Membrane Dynamics ◽

Hematopoietic Stem ◽

Murine Bone Marrow ◽

Cell Functions ◽

Granule Membrane

Mast cells are derived from hematopoietic stem cells and play important roles in allergic responses. Mast cells are long-lived compared with other granular cell types. Since the response of the individual mast cell after FcεRI-induced degranulation is unclear, the aim of this study was to analyze morphological changes in individual mast cells after restimulation. To observe plasma and granule membrane dynamics, AcGFP-actb (β-actin) and DsRed-monomer (DRM)- CD63 fusion constructs were introduced into bone marrow-derived mast cells (BMMCs). Furthermore, AcGFP-CD63 and DRM-Cma1 (mMCP-5) were introduced into BMMCs. Re-stimulation resulted in increased β-hexosaminidase release and cytokine mRNA expression similar to those observed during initial stimulation. Moreover, expression of FcεRI on BMMCs 24 h after initial stimulation was similar to that measured before initial stimulation. Changes in morphology of the plasma membrane and colocalization of granules and plasma membrane were observed after initial stimulation. BMMCs returned to normal 120 min after the initial stimulation. These phenomena were also observed in BMMCs after re-stimulation. BMMC chymase content decreased 20 min after stimulation but returned to near normal 24 h after stimulation. These findings suggest that mast cell functions can be maintained and that these cells can be repeatedly degranulated after FcεRI-mediated stimulation.

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Demonstration of distinct pathways of mast cell‐dependent inhibition of Treg generation using murine bone marrow‐derived mast cells

Allergy ◽

10.1111/all.14267 ◽

2020 ◽

Vol 75 (8) ◽

pp. 2088-2091

Author(s):

Sara Benede ◽

Leticia Tordesillas ◽

Cecilia Berin

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Mast Cells ◽

Murine Bone Marrow ◽

Dependent Inhibition

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Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis

Thorax ◽

10.1136/thoraxjnl-2018-211516 ◽

2019 ◽

Vol 74 (5) ◽

pp. 455-465 ◽

Cited By ~ 18

Author(s):

Chiko Shimbori ◽

Chandak Upagupta ◽

Pierre-Simon Bellaye ◽

Ehab A Ayaub ◽

Seidai Sato ◽

...

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Mast Cells ◽

Pulmonary Fibrosis ◽

Transforming Growth Factor ◽

Mechanical Stretch ◽

Mast Cell Degranulation ◽

Mean Difference ◽

Peritoneal Mast Cell ◽

Tgf Β1

BackgroundThe role of mast cells accumulating in idiopathic pulmonary fibrosis (IPF) lungs is unknown.ObjectivesWe investigated the effect of fibrotic extracellular matrix (ECM) on mast cells in experimental and human pulmonary fibrosis.ResultsIn IPF lungs, mast cell numbers were increased and correlated with disease severity (control vs 60%<FVC<90%, mean difference=-222.7, 95% CI −386.3 to −59.2, p=0.004; control vs FVC<60%, mean difference=−301.7, 95% CI of difference −474.1 to −129.34, p=0.0001; FVC>90% vs 60%<FVC<90%, mean difference=−189.6, 95% CI of difference −353.1 to −26.03, p=0.017; FVC>90% vs FVC<60%, mean difference=−268.6, 95% CI of difference −441.0 to −96.17, p=0.0007). Plasma tryptase levels were increased in IPF and negatively correlated with FVC (control vs FVC<60%, mean difference=−17.12, 95% CI of difference −30.02 to −4.22, p=0.006: correlation curves R=−0.045, p=0.025). In a transforming growth factor (TGF)-β1-induced pulmonary fibrosis model, chymase-positive and tryptase-positive mast cells accumulated in fibrotic lung. Lung tissue was decellularised and reseeded with bone marrow or peritoneum-derived mast cells; cells on fibrotic ECM released more TGF-β1 compared with normal ECM (active TGF-β1: bone marrow-derived mast cell (BMMC)-DL vs BMMC-TGF-β1 p=0.0005, peritoneal mast cell (PMC)-DL vs PMC-TGF-β1 p=0.0003, total TGF-β1: BMMC-DL vs BMMC-TGF-β1 p=0.013, PMC-DL vs PMC-TGF-β1 p=0.001). Mechanical stretch of lungs caused mast cell degranulation; mast cell stabilisers inhibited degranulation (histamine: cont vs doxantrazole p=0.004, β-hexosaminidase: cont vs doxantrazole, mean difference=1.007, 95% CI of difference 0.2700 to 1.744, p=0.007) and TGF-β1 activation (pSmad2/Smad2: cont vs dox p=0.006). Cromoglycate attenuated pulmonary fibrosis in rats (collagen: phosphate-buffered saline (PBS) vs cromoglycate p=0.036, fibrotic area: PBS vs cromoglycate p=0.031).ConclusionThis study suggests that mast cells may contribute to the progression of pulmonary fibrosis.

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Preferential expression of interleukin-12 or interleukin-4 by murine bone marrow mast cells derived in mast cell growth factor or interleukin-3

European Journal of Immunology ◽

10.1002/eji.1830240408 ◽

1994 ◽

Vol 24 (4) ◽

pp. 822-826 ◽

Cited By ~ 46

Author(s):

Tracey J. Smith ◽

Lori A. Ducharme ◽

John H. Weis

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Growth Factor ◽

Mast Cells ◽

Cell Growth ◽

Interleukin 4 ◽

Interleukin 12 ◽

Murine Bone Marrow ◽

Preferential Expression ◽

Mast Cell Growth Factor

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Increased Growth Promoting But Not Mast Cell Degranulation Potential of a Covalent Dimer of c-Kit Ligand

Blood ◽

10.1182/blood.v90.10.3874 ◽

1997 ◽

Vol 90 (10) ◽

pp. 3874-3883 ◽

Cited By ~ 14

Author(s):

Karl H. Nocka ◽

Beth A. Levine ◽

Jone-Lone Ko ◽

Peter M. Burch ◽

Bryan E. Landgraf ◽

...

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Mast Cells ◽

Cell Activation ◽

Mast Cell Activation ◽

Native Form ◽

Murine Bone Marrow ◽

Kit Ligand ◽

Growth Promoting

Abstract The native form of soluble c-kit ligand (KL) is a noncovalent dimer. We have isolated a soluble, disulfide-linked dimer of murine KL (KL-CD) by expressing KL in Escherichia coli and refolding the denatured protein under conditions that promote the formation of both noncovalent dimers (KL-NC) and KL-CD. KL-CD exhibits a 10- to 15-fold increase in the ability to stimulate the growth of both the human megakaryocytic cell line MO7e and murine bone marrow-derived mast cells relative to KL-NC. Colony-forming assays of murine bone marrow progenitor cells also reflected this increased potency. However, KL-CD and KL-NC are equally able to prime mast cells for enhanced IgE-dependent degranulation in vitro and activate mast cells in vivo. Improving the growth-promoting activity of KL without changing its mast cell activation potential suggests that KL-CD or a related molecule could be administered in the clinic at doses that stimulate hematopoietic recovery while avoiding significant mast cell activation.

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