scholarly journals Distinct roles of sphingosine kinases 1 and 2 in human mast-cell functions

Blood ◽  
2008 ◽  
Vol 111 (8) ◽  
pp. 4193-4200 ◽  
Author(s):  
Carole A. Oskeritzian ◽  
Sergio E. Alvarez ◽  
Nitai C. Hait ◽  
Megan M. Price ◽  
Sheldon Milstien ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Critical Role ◽  
Human Mast Cell ◽  
Lipid Mediator ◽  
Cell Functions ◽  
Tnf Α ◽  
Sphingosine 1 Phosphate ◽  
Enhanced Secretion ◽  
Sphingosine Kinases

Abstract Sphingosine-1-phosphate (S1P) is now emerging as a potent lipid mediator produced by mast cells that contributes to inflammatory and allergic responses. In contrast to its weak effect on degranulation of murine mast cells, S1P potently induced degranulation of the human LAD2 mast-cell line and cord blood–derived human mast cells (hMCs). S1P also stimulated production and secretion of cytokines, TNF-α and IL-6, and markedly enhanced secretion of a chemokine, CCL2/MCP-1, important modulators of inflammation. S1P is produced in mast cells by the 2 sphingosine kinases, SphK1 and SphK2. SphK1 but not SphK2 plays a critical role in IgE/Ag-induced degranulation, migration toward antigen, and CCL2 secretion from hMCs, as determined by specifically down-regulating their expression. However, both isoenzymes were required for efficient TNF-α secretion. Taken together, our data suggest that differential formation of S1P by SphK1 and SphK2 has distinct and important actions in hMCs.

scholarly journals Essential roles of sphingosine-1–phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema

2010 ◽  
Vol 207 (3) ◽  
pp. 465-474 ◽  
Author(s):  
Carole A. Oskeritzian ◽  
Megan M. Price ◽  
Nitai C. Hait ◽  
Dmitri Kapitonov ◽  
Yves T. Falanga ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Pulmonary Edema ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Critical Role ◽  
Mast Cell Activation ◽  
Human Mast Cell ◽  
Cell Functions ◽  
Sphingosine 1 Phosphate

Systemic exacerbation of allergic responses, in which mast cells play a critical role, results in life-threatening anaphylactic shock. Sphingosine-1–phosphate (S1P), a ligand for a family of G protein–coupled receptors, is a new addition to the repertoire of bioactive lipids secreted by activated mast cells. Yet little is known of its role in human mast cell functions and in anaphylaxis. We show that S1P2 receptors play a critical role in regulating human mast cell functions, including degranulation and cytokine and chemokine release. Immunoglobulin E–triggered anaphylactic responses, including elevation of circulating histamine and associated pulmonary edema in mice, were significantly attenuated by the S1P2 antagonist JTE-013 and in S1P2-deficient mice, in contrast to anaphylaxis induced by administration of histamine or platelet-activating factor. Hence, S1P and S1P2 on mast cells are determinants of systemic anaphylaxis and associated pulmonary edema and might be beneficial targets for anaphylaxis attenuation and prophylaxis.

scholarly journals Divergent effects of acute and prolonged interleukin 33 exposure on mast cell IgE-mediated functions

2018 ◽  
Author(s):  
Elin Rönnberg ◽  
Avan Ghaib ◽  
Carlos Ceriol ◽  
Mattias Enoksson ◽  
Michel Arock ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Prolonged Exposure ◽  
Allergic Inflammation ◽  
Acute Effect ◽  
Receptor Expression ◽  
Human Mast Cell ◽  
Interleukin 33 ◽  
Cell Functions ◽  
Ige Mediated

AbstractBackgroundEpithelial cytokines, including IL-33 and TSLP, have attracted interest because of their roles in chronic allergic inflammation-related conditions such as asthma. Mast cells are one of the major targets of IL-33, to which they respond by secreting cytokines. Most studies performed thus far have investigated the acute effects of IL-33 on mast cells.ObjectiveThe objective of this study is to investigate how acute versus prolonged exposure of human mast cells to IL-33 and TSLP affects mediator synthesis and IgE-mediated activation.MethodsHuman lung mast cells (HLMCs), cord blood-derived mast cells (CBMCs), and the ROSA mast cell line were used for this study. Surface receptor expression and the levels of mediators were measured after treatment with IL-33 and/or TSLP.ResultsIL-33 induced the acute release of cytokines. Prolonged exposure to IL-33 increased while TSLP reduced intracellular levels of tryptase. Acute IL-33 treatment strongly potentiated IgE-mediated activation. In contrast, four days of exposure to IL-33 decreased IgE-mediated activation, an effect that was accompanied by a reduction in FcεRI expression.Conclusion & Clinical RelevanceWe show that IL-33 plays dual roles for mast cell functions. The acute effect includes cytokine release and the potentiation of IgE-mediated degranulation, whereas prolonged exposure to IL-33 reduces IgE-mediated activation. We conclude that mast cells act quickly in response to the alarmin IL-33 to initiate an acute inflammatory response, whereas extended exposure to IL-33 during prolonged inflammation reduces IgE-mediated responses. This negative feedback effect suggests the presence of a novel IL-33 mediated regulatory pathway that modulates IgE-induced human mast cell responses.

scholarly journals Roles of IgE and Histamine in Mast Cell Maturation

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2170
Author(s):  
Satoshi Tanaka ◽  
Kazuyuki Furuta
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Cell Maturation ◽  
Tissue Type ◽  
Human Mast Cell ◽  
Therapeutic Effects ◽  
Serum Ige ◽  
Cell Functions ◽  
Histamine Synthesis

Mast cells are activated upon immunoglobulin E (IgE)-mediated antigen stimulation, and release a wide variety of mediators, including histamine to trigger inflammatory responses. The surface expression levels of Fcε receptor I (FcεRI), a high affinity receptor of IgE, were found to be positively regulated by IgE. IgE could protect murine cultured mast cells from apoptotic cell death induced by the deprivation of interleukin-3 and a certain kind of IgE could activate immature mast cells in the absence of antigens, leading to the release of pro-inflammatory cytokines and a transient increase in histamine synthesis. Histamine synthesis in mast cells was found to be required for the maturation of murine connective tissue-type mast cells, raising the possibility that IgE indirectly modulates local mast cell maturation. Although it remains controversial to what extent this concept of “monomeric IgE effects” could have relevance in the modulation of human mast cell functions, the therapeutic effects of anti-IgE antibodies might be accounted for in terms of the decreased serum IgE concentrations. Because drastic increases in serum IgE concentrations are often observed in patients with atopic dermatitis and chronic urticaria, a close investigation of the roles of IgE in mast cell maturation should contribute to development of novel therapeutic approaches for these inflammatory diseases.

Inhibitory Effects of BiRyuChe-Bang on Mast Cell-Mediated Allergic Reactions and Inflammatory Cytokines Production

2013 ◽  
Vol 41 (06) ◽  
pp. 1267-1282 ◽  
Author(s):  
Phil-Dong Moon ◽  
Il Sang Choi ◽  
Ji-Hyun Go ◽  
Byong-Joo Lee ◽  
Sang Woo Kang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Inflammatory Cytokines ◽  
Medical Center ◽  
Human Mast Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Allergic Reactions ◽  
Linalyl Acetate ◽  
Tnf Α

BiRyuChe-bang (BRC) is a Korean prescription medicine, which has been used to treat allergic rhinitis at Kyung Hee Medical Center. In this work, we investigated the effects of BRC on mast cell-mediated allergic reactions and inflammatory cytokines production, and identified the active component of BRC. Histamine release was measured from rat peritoneal mast cells (RPMCs). Ear swelling and passive cutaneous anaphylaxis (PCA) were examined in mouse models. Phorbol 12-myristate 13-acetate (PMA) plus A23187-induced inflammatory cytokines production was measured using enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used for the expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8. Activation of nuclear factor (NF)-κB was analyzed by Western blotting. BRC significantly inhibited the compound 48/80-induced ear swelling response, histamine release from RPMCs, PCA activated by anti-dinitrophenyl IgE, and PMA plus A23187-induced inflammatory cytokines production (p < 0.05). In addition, BRC dose-dependently inhibited the mRNA expressions of TNF-α, IL-6, and IL-8 as well as the activation of NF-κB in a human mast cell line, HMC-1 cells. BRC inhibited the levels of TNF-α and IL-6 in mice induced with PCA. Several components of BRC, such as 1,8-Cineole, Linalool, Linalyl acetate, α-Pinene, and α-Terpineol, significantly inhibited the release of histamine from RPMCs (p < 0.05). Among these components, Linalyl acetate was the most effective for inhibiting histamine release. These results indicate that BRC has a potential regulatory effect on allergic and inflammatory reactions mediated by mast cells.

scholarly journals Hypoxia modulates human mast cell adhesion to hyaluronic acid

2021 ◽  
Author(s):  
Joanna Pastwińska ◽  
Aurelia Walczak-Drzewiecka ◽  
Elżbieta Kozłowska ◽  
Enjuro Harunari ◽  
Marcin Ratajewski ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mast Cell ◽  
Hyaluronic Acid ◽  
Cell Adhesion ◽  
Mast Cells ◽  
Immune Cell ◽  
Human Mast Cell ◽  
Dependent Manner ◽  
Cell Functions ◽  
Extracellular Matrix Components

AbstractHypoxia is an inherent factor in the inflammatory process and is important in the regulation of some immune cell functions, including the expression of mast cell pro- and anti-inflammatory mediators. Hypoxia also influences cell adhesion to the extracellular matrix (ECM). Hyaluronic acid is one of the major components of the ECM that is involved in inflammatory and tissue regeneration processes in which mast cells play a prominent role. This prompted us to investigate the effects of hypoxia on the expression of hyaluronic acid receptors in mast cells and mast cell adhesion to this ECM component. We found that human LAD2 mast cells spontaneously adhered to hyaluronic acid in a CD44-dependent manner and that reduced oxygen concentrations inhibited or even completely abolished this adhesion process. The mechanism of hypoxia downregulation of mast cell adhesion to hyaluronic acid did not involve a decrease in CD44 expression and hyaluronidase-mediated degradation of adhesion substrates but rather conformational changes in the avidity of CD44 to hyaluronic acid. Hypoxia-mediated regulation of mast cell adhesion to extracellular matrix components might be involved in the pathogenic accumulation of mast cells observed in the course of certain diseases including rheumatoid arthritis and cancer.

scholarly journals Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.

1991 ◽  
Vol 174 (4) ◽  
pp. 821-825 ◽  
Author(s):  
H Mizutani ◽  
N Schechter ◽  
G Lazarus ◽  
R A Black ◽  
T S Kupper
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Secretory Granules ◽  
Interleukin 1 ◽  
Critical Role ◽  
Biologically Active ◽  
Surrounding Tissue ◽  
Human Mast Cell ◽  
Interleukin 1 Beta ◽  
Mast Cell Chymase

Secretory granules of human dermal mast cells contain a chymotrypsin-like serine proteinase called chymase. In this study, we demonstrate that the inactive cytokine, 31 kD interleukin 1 beta (IL-1 beta), can be converted rapidly to an 18 kD biologically active species by human mast cell chymase. The product formed is three amino acids longer at the amino terminus than the mature IL-1 beta produced by peripheral blood mononuclear cells and has comparable biological activity. Because chymase is a secretory granule constituent, it is likely to be released into the surrounding tissue when mast cells degranulate. It is also known that non-bone marrow derived cells resident in skin (keratinocytes, fibroblasts) produce but do not process 31 kD IL-1 beta. In this context, chymase may be a potent activator of locally produced 31 kD IL-1 beta. Mast cells lie in close apposition to blood vessels in dermis; therefore, chymase mediated conversion of 31 kD IL-1 beta might be expected to have a critical role in the initiation of the inflammatory response in skin.

In vitro inhibitory effect of rupatadine on histamine and TNF-α release from dispersed canine skin mast cells and the human mast cell line HMC-1

2000 ◽  
Vol 49 (7) ◽  
pp. 355-360 ◽  
Author(s):  
M. Queralt ◽  
P. Brazís ◽  
M. Merlos ◽  
F. de Mora ◽  
A. Puigdemont
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Line ◽  
Inhibitory Effect ◽  
Human Mast Cell ◽  
Tnf Α ◽  
Mast Cell Line

scholarly journals Transactivation of Sphingosine-1–Phosphate Receptors by FcεRI Triggering Is Required for Normal Mast Cell Degranulation and Chemotaxis

2004 ◽  
Vol 199 (7) ◽  
pp. 959-970 ◽  
Author(s):  
Puneet S. Jolly ◽  
Meryem Bektas ◽  
Ana Olivera ◽  
Claudia Gonzalez-Espinosa ◽  
Richard L. Proia ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Sphingosine Kinase ◽  
Cross Linking ◽  
Cell Functions ◽  
Sphingosine 1 Phosphate ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
And Migration ◽  
Cytoskeletal Rearrangements

Mast cells secrete various substances that initiate and perpetuate allergic responses. Cross-linking of the high-affinity receptor for IgE (FcεRI) in RBL-2H3 and bone marrow–derived mast cells activates sphingosine kinase (SphK), which leads to generation and secretion of the potent sphingolipid mediator, sphingosine-1–phosphate (S1P). In turn, S1P activates its receptors S1P1 and S1P2 that are present in mast cells. Moreover, inhibition of SphK blocks FcεRI-mediated internalization of these receptors and markedly reduces degranulation and chemotaxis. Although transactivation of S1P1 and Gi signaling are important for cytoskeletal rearrangements and migration of mast cells toward antigen, they are dispensable for FcεRI-triggered degranulation. However, S1P2, whose expression is up-regulated by FcεRI cross-linking, was required for degranulation and inhibited migration toward antigen. Together, our results suggest that activation of SphKs and consequently S1PRs by FcεRI triggering plays a crucial role in mast cell functions and might be involved in the movement of mast cells to sites of inflammation.

scholarly journals Disrupted Lipid Raft Shuttling of FcεRI by n-3 Polyunsaturated Fatty Acid Is Associated With Ligation of G Protein-Coupled Receptor 120 (GPR120) in Human Mast Cell Line LAD2

2020 ◽  
Vol 7 ◽  
Author(s):  
Xiaofeng Wang ◽  
Ramses Ilarraza ◽  
Brian P. Tancowny ◽  
Syed Benazir Alam ◽  
Marianna Kulka
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Line ◽  
G Protein ◽  
Lipid Raft ◽  
Human Mast Cell ◽  
G Protein Coupled Receptor ◽  
Cell Functions ◽  
Mast Cell Line ◽  
G Protein Coupled

n-3 polyunsaturated fatty acids (PUFA) influences a variety of disease conditions, such as hypertension, heart disease, diabetes, cancer and allergic diseases, by modulating membrane constitution, inhibiting production of proinflammatory eicosanoids and cytokines, and binding to cell surface and nuclear receptors. We have previously shown that n-3 PUFA inhibit mast cell functions by disrupting high affinity IgE receptor (FcεRI) lipid raft partitioning and subsequent suppression of FcεRI signaling in mouse bone marrow-derived mast cells. However, it is still largely unknown how n-3 PUFA modulate human mast cell function, which could be attributed to multiple mechanisms. Using a human mast cell line (LAD2), we have shown similar modulating effects of n-3 PUFA on FcεRI lipid raft shuttling, FcεRI signaling, and mediator release after cell activation through FcεRI. We have further shown that these effects are at least partially associated with ligation of G protein-coupled receptor 120 expressed on LAD2 cells. This observation has advanced our mechanistic knowledge of n-3 PUFA's effect on mast cells and demonstrated the interplay between n-3 PUFA, lipid rafts, FcεRI, and G protein-coupled receptor 120. Future research in this direction may present new targets for nutritional intervention and therapeutic agents.

scholarly journals The transcriptional program, functional heterogeneity, and clinical targeting of mast cells

2017 ◽  
Vol 214 (9) ◽  
pp. 2491-2506 ◽  
Author(s):  
Gökhan Cildir ◽  
Harshita Pant ◽  
Angel F. Lopez ◽  
Vinay Tergaonkar
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Small Population ◽  
Transcriptional Program ◽  
Cell Functions ◽  
New Concepts ◽  
Health And Disease ◽  
Ige Mediated

Mast cells are unique tissue-resident immune cells that express an array of receptors that can be activated by several extracellular cues, including antigen–immunoglobulin E (IgE) complexes, bacteria, viruses, cytokines, hormones, peptides, and drugs. Mast cells constitute a small population in tissues, but their extraordinary ability to respond rapidly by releasing granule-stored and newly made mediators underpins their importance in health and disease. In this review, we document the biology of mast cells and introduce new concepts and opinions regarding their role in human diseases beyond IgE-mediated allergic responses and antiparasitic functions. We bring to light recent discoveries and developments in mast cell research, including regulation of mast cell functions, differentiation, survival, and novel mouse models. Finally, we highlight the current and future opportunities for therapeutic intervention of mast cell functions in inflammatory diseases.

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