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

Allergy ◽  
2020 ◽  
Vol 75 (8) ◽  
pp. 2088-2091
Author(s):  
Sara Benede ◽  
Leticia Tordesillas ◽  
Cecilia Berin
2015 ◽  
Vol 8 (1) ◽  
pp. 14-22
Author(s):  
Masahiro Kaneko ◽  
Arisa Yamada

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.


Blood ◽  
1997 ◽  
Vol 90 (10) ◽  
pp. 3874-3883 ◽  
Author(s):  
Karl H. Nocka ◽  
Beth A. Levine ◽  
Jone-Lone Ko ◽  
Peter M. Burch ◽  
Bryan E. Landgraf ◽  
...  

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.


2005 ◽  
Vol 78 (3) ◽  
pp. 605-611 ◽  
Author(s):  
Junko Noguchi ◽  
Etsushi Kuroda ◽  
Uki Yamashita

2008 ◽  
Vol 295 (5) ◽  
pp. H1825-H1833 ◽  
Author(s):  
Tyler H. Rork ◽  
Kori L. Wallace ◽  
Dylan P. Kennedy ◽  
Melissa A. Marshall ◽  
Amy R. Lankford ◽  
...  

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.


Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 573-580 ◽  
Author(s):  
Y Kanakura ◽  
A Kuriu ◽  
N Waki ◽  
T Nakano ◽  
H Asai ◽  
...  

Abstract Two different types of cells in the peritoneal cavity of mice produce mast cell colonies in methylcellulose. “Large” mast cell colonies are produced by bone marrow-derived precursors resembling lymphoid cells by light microscopy (L-CFU-Mast), whereas “medium” and “small” mast cell colonies are produced by morphologically identifiable mast cells (M-CFU- Mast and S-CFU-Mast, respectively). In the present study we eradicated peritoneal mast cells by intraperitoneal (IP) injection of distilled water. The regeneration process was investigated to clarify the relationship between L-CFU-Mast, M-CFU-Mast, and S-CFU-Mast. After injection of distilled water, M-CFU-Mast and S-CFU-Mast disappeared, but L-CFU-Mast increased, and then M-CFU-Mast and S-CFU-Mast appeared, suggesting the presence of a hierarchic relationship. When purified peritoneal mast cells were injected two days after the water injection, the L-CFU-Mast did not increase. In the peritoneal cavity of WBB6F1-+/+ mice that had been lethally irradiated and rescued by bone marrow cells of C57BL/6-bgJ/bgJ (beige, Chediak-Higashi syndrome) mice, L-CFU-Mast were of bgJ/bgJ type, but M-CFU-Mast and S-CFU-Mast were of +/+ type. The injection of distilled water to the radiation chimeras resulted in the development of bgJ/bgJ-type M-CFU-Mast and then S-CFU-Mast. The presence of mast cells appeared to suppress the recruitment of L-CFU- Mast from the bloodstream and to inhibit the differentiation of L-CFU- Mast to M-CFU-Mast.


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