scholarly journals Equine Airway Mast Cells are Sensitive to Cell Death Induced by Lysosomotropic Agents

2017 ◽  
Vol 85 (1) ◽  
pp. 30-34 ◽  
Author(s):  
S. Wernersson ◽  
M. Riihimäki ◽  
G. Pejler ◽  
I. Waern
Keyword(s):  
Cell Death ◽  
Mast Cells ◽  
Lysosomotropic Agents

scholarly journals ETosis: A Microbicidal Mechanism beyond Cell Death

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Anderson B. Guimarães-Costa ◽  
Michelle T. C. Nascimento ◽  
Amanda B. Wardini ◽  
Lucia H. Pinto-da-Silva ◽  
Elvira M. Saraiva
Keyword(s):  
Cell Death ◽  
Mast Cells ◽  
Cell Types ◽  
Neutrophil Extracellular Traps ◽  
Protozoan Parasites ◽  
Extracellular Milieu ◽  
Extracellular Traps ◽  
Cytoplasmic Proteins

Netosis is a recently described type of neutrophil death occurring with the release to the extracellular milieu of a lattice composed of DNA associated with histones and granular and cytoplasmic proteins. These webs, initially named neutrophil extracellular traps (NETs), ensnare and kill microorganisms. Similarly, other cell types, such as eosinophils, mast cells, and macrophages, can also dye by this mechanism; thus, it was renamed as ETosis, meaning death with release of extracellular traps (ETs). Here, we review the mechanism of NETosis/etosis, emphasizing its role in diseases caused by protozoan parasites, fungi, and viruses.

scholarly journals Indirect involvement of allergen-captured mast cells in antigen presentation

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1489-1496 ◽  
Author(s):  
Taku Kambayashi ◽  
Jan D. Baranski ◽  
Rebecca G. Baker ◽  
Tao Zou ◽  
Eric J. Allenspach ◽  
...  
Keyword(s):  
Cell Death ◽  
Mast Cell ◽  
T Cell ◽  
Mast Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Complex Class ◽  
Cell Responses ◽  
Histocompatibility Complex

Abstract It is generally thought that mast cells influence T-cell activation nonspecifically through the release of inflammatory mediators. In this report, we provide evidence that mast cells may also affect antigen-specific T-cell responses by internalizing immunoglobulin E–bound antigens for presentation to antigen-specific T cells. Surprisingly, T-cell activation did not require that mast cells express major histocompatibility complex class II, indicating that mast cells were not involved in the direct presentation of the internalized antigens. Rather, the antigen captured by mast cells is presented by other major histocompatibility complex class II+ antigen-presenting cells. To explore how this may occur, we investigated the fate of mast cells stimulated by antigen and found that FcϵRI crosslinking enhances mast cell apoptosis. Cell death by antigen-captured mast cells was required for efficient presentation because protection of mast cell death significantly decreased T-cell activation. These results suggest that mast cells may be involved in antigen presentation by acting as an antigen reservoir after antigen capture through specific immunoglobulin E molecules bound to their FcϵRI. This mechanism may contribute to how mast cells impact the development of T-cell responses.

Mast Cells Prevent Dexamethasone-Induced Cell Death of Cultured Fibroblasts

2014 ◽  
Vol 133 (5) ◽  
pp. 638e-644e ◽  
Author(s):  
Theodore T. Foley ◽  
H. Paul Ehrlich
Keyword(s):  
Cell Death ◽  
Mast Cells ◽  
Cultured Fibroblasts

Histone Deacetylase Inhibitor SAHA Mediates Epigenetic Silencing of KIT D816V Mutated Systemic Mastocytosis Primary Mast Cells and Selective Apoptosis of Mutated Mast Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2834-2834 ◽  
Author(s):  
Hani Abdulkadir ◽  
Jennine Grootens ◽  
Matilda Kjellander ◽  
Eva Hellstrom Lindberg ◽  
Gunnar Nilsson ◽  
...  
Keyword(s):  
Cell Death ◽  
Mast Cell ◽  
Mast Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Conflicts Of Interest ◽  
Systemic Mastocytosis ◽  
Specific Treatment ◽  
Epigenetic Silencing ◽  
Kit Receptor

Abstract Systemic mastocytosis (SM) is a myeloproliferative disease for which there is currently no specific therapy. Over 90% of the patients carry the D816V point mutation that renders the KIT receptor constitutively active. In the current study, we assessed the sensitivity of mast cell line HMC1.2 and primary SM patient mast cells to histone deacetylase inhibitors, and found that SAHA is most efficient. SAHA induced a rapid downregulation of KIT mRNA, with a subsequent reduction in total KIT protein as well as cell surface KIT. This was followed by major mast cell apoptosis. Primary SM patient mast cells cultured ex vivo were even more sensitive to SAHA than HMC1.2 cells, whereas healthy subject mast cells were unaffected. There was a correlation between cell death and SM disease severity, where cell death was more pronounced in the case of aggressive disease, with almost 100% cell death among mast cells from the mast cell leukemia patient. Using ChIP qPCR, we found that the level of active chromatin mark H3K18ac/totalH3 decreased significantly in the KIT region, due to an increase in H3 density. This epigenetic silencing was specific to the KIT region and not seen in control genes upstream and downstream of KIT. Primary analysis of ChIP-seq data for histone marks H3K4me3 and H3K27me3, demonstrates a downregulation of transcription factors involved in activation of KIT receptor, such as MAPK, for the SAHA treated samples. This indicates an indirect epigenetic silencing of KIT. Our results therefore demonstrate that SAHA epigenetically silences KIT, and work is ongoing to elucidate the exact mechanisms of KIT regulation. Altogether, SAHA maybe a specific treatment for SM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Protection From Apoptosis by Steel Factor But Not Interleukin-3 Is Reversed Through Blockade of Calcium Influx

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 1891-1900 ◽  
Author(s):  
Jennifer L. Gommerman ◽  
Stuart A. Berger
Keyword(s):  
Cell Death ◽  
Mast Cells ◽  
Cell Survival ◽  
Calcium Influx ◽  
Caspase Inhibitors ◽  
Steel Factor ◽  
Interleukin 3 ◽  
Kit Receptor ◽  
Induced Apoptosis ◽  
P815 Mastocytoma

Abstract Steel factor (SLF), the ligand for the c-Kit receptor, protects hemopoietic progenitors and mast cells from apoptosis. We show here that protection of 32D-Kit cells or mast cells from apoptosis by SLF is abrogated through concurrent inhibition of Ca2+influx. In contrast, cell survival promoted by interleukin-3 is not affected by Ca2+ influx blockers. In the presence of blockers, increasing stimulation by SLF leads to greater levels of cell death in the population, indicating that it is the combination of activation by SLF with concurrent blockade of Ca2+ influx that results in apoptosis. The p815 mastocytoma, which expresses a mutated, constitutively active c-kit receptor, dies apoptotically in the presence of Ca2+ influx blockers alone. Ionomycin protects cells from SLF plus blocker-induced apoptosis, confirming specificity for Ca2+ ion blockade in cell death induction. Overexpression of bcl-2, which protects 32D-Kit cells from factor withdrawal, does not protect cells from apoptosis by SLF plus blocker. In contrast, caspase inhibitors YVAD-CHO, DEVD-FMK, and Boc-Asp-FMK protect cells from SLF plus blocker-induced death. These observations highlight the importance of SLF-stimulated Ca2+ influx in the protection of cells from apoptosis and demonstrate a new mechanism for inducing bcl-2 insensitive, caspase-dependent apoptosis through the combination of SLF stimulation with Ca2+ influx blockade.

scholarly journals α-Melanocyte-stimulating hormone induces cell death in mast cells: involvement of NF-κB

FEBS Letters ◽  
2003 ◽  
Vol 549 (1-3) ◽  
pp. 87-93 ◽  
Author(s):  
Abira Sarkar ◽  
Yashin Sreenivasan ◽  
Sunil K Manna
Keyword(s):  
Cell Death ◽  
Mast Cells ◽  
Melanocyte Stimulating Hormone ◽  
Stimulating Hormone

scholarly journals Phagocytic Cell Killing Mediated by Secreted Cytotoxic Factors of Vibrio cholerae

2000 ◽  
Vol 68 (9) ◽  
pp. 4930-4937 ◽  
Author(s):  
Vasu Punj ◽  
Olga Zaborina ◽  
Neelam Dhiman ◽  
Kim Falzari ◽  
M. Bagdasarian ◽  
...  
Keyword(s):  
Cell Death ◽  
Mast Cell ◽  
Mast Cells ◽  
Vibrio Cholerae ◽  
Growth Medium ◽  
Adenylate Kinase ◽  
Morphological Changes ◽  
Nucleoside Diphosphate Kinase ◽  
Phagocytic Cell ◽  
Nuclear Fragmentation

ABSTRACT Vibrio cholerae strain VB1 secretes a number of enzymes into the outside medium that utilize ATP as a substrate. Such enzymes are found in the outside medium during the mid-log phase of growth, when the optical density at 650 nm is about 0.4, and they demonstrate nucleoside diphosphate kinase (Ndk), 5′ nucleotidase, and adenylate kinase (Ak) activities. We report that the filtered growth medium ofV. cholerae, as well as the flowthrough fraction of a green Sepharose column during fractionation of the growth medium, had very little cytotoxicity by itself towards macrophages and mast cells but exhibited significant cytotoxicity in the presence of exogenous ATP. Such fractions, harboring 5′ nucleotidase, Ndk, and presumably other ATP-utilizing enzymes, demonstrated enhanced macrophage and mast cell death; periodate-oxidized-ATP (oATP)-treated macrophage and mast cells or such cells exposed to 0.1 mM Mg2+, where surface-associated P2Z receptors could not be activated, were not susceptible to subsequent ATP addition. Microscopic visualization of mast cells clearly demonstrated cell morphological changes such as swelling, vacuolization, and nuclear fragmentation following treatment with ATP and the growth medium of V. cholerae; however, these effects were suppressed if the mast cells were pretreated with oATP. These results strongly imply that the secreted ATP-utilizing enzymes of V. cholerae modulate the external ATP levels of the macrophage and mast cells, leading to their accelerated death, presumably through activation of P2Z receptors. Thus, development of inhibitors for such enzymes may reduce the level of V. cholerae infection; alternatively, mutations in such genes may eliminate V. cholerae survival in the gut and contribute to a safer live vaccine.

scholarly journals Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Sultan Alanazi ◽  
Fabio Rabelo Melo ◽  
Gunnar Pejler
Keyword(s):  
Cell Death ◽  
Mast Cell ◽  
Mast Cells ◽  
Epigenetic Modification ◽  
Secretory Granules ◽  
Leukemia Cells ◽  
Human Mast Cell ◽  
Cell Leukemia ◽  
Core Histones ◽  
Mast Cell Leukemia

Mast cells are immune cells that store large amounts of mast cell-restricted proteases in their secretory granules, including tryptase, chymase and carboxypeptidase A3. In mouse mast cells, it has been shown that tryptase, in addition to its canonical location in secretory granules, can be found in the nuclear compartment where it can impact on core histones. Here we asked whether tryptase can execute core histone processing in human mast cell leukemia cells, and whether tryptase thereby can affect the epigenetic modification of core histones. Our findings reveal that triggering of cell death in HMC-1 mast cell leukemia cells is associated with extensive cleavage of core histone 3 (H3) and more restricted cleavage of H2B. Tryptase inhibition caused a complete blockade of such processing. Our data also show that HMC-1 cell death was associated with a major reduction of several epigenetic histone marks, including H3 lysine-4-mono-methylation (H3K4me1), H3K9me2, H3 serine-10-phosphorylation (H3S10p) and H2B lysine-16-acetylation (H2BK16ac), and that tryptase inhibition reverses the effect of cell death on these epigenetic marks. Further, we show that tryptase is present in the nucleus of both viable and dying mast cell leukemia cells. In line with a role for tryptase in regulating nuclear events, tryptase inhibition caused increased proliferation of the mast cell leukemia cells. Altogether, the present study emphasizes a novel principle for how epigenetic modification of core histones is regulated, and provides novel insight into the biological function of human mast cell tryptase.

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