scholarly journals Kinase suppressor of Ras (KSR1) modulates multiple kit-ligand−dependent mast cell functions

2011 ◽  
Vol 39 (10) ◽  
pp. 969-976 ◽  
Author(s):  
Mia Chen ◽  
Sarah Burgin ◽  
Karl Staser ◽  
Yongzheng He ◽  
Xiaohong Li ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Functions ◽  
Kit Ligand ◽  
Kinase Suppressor Of Ras

Kinase Suppressor of Ras Plays a Critical Role in Modulating Inflammatory Mast Cell Functions.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2407-2407
Author(s):  
Meng Chen ◽  
Whitney Horn ◽  
Xiaohong Li ◽  
Scott Knowles ◽  
David Ingram ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Western Blots ◽  
Cell Functions ◽  
Kit Ligand ◽  
Fold Reduction ◽  
Kinase Suppressor Of Ras ◽  
And Migration

Abstract The Raf/MEK/extracellular signal-regulated kinase (ERK) kinase cascade and the Ras-PI3-K-Akt pathways are intricately regulated and evolutionarily conserved pathways that have been implicated in specialized cellular functions including proliferation, differentiation, survival and degranulation. Recent data suggest that the strength and duration of these signals is maintained by extracellular growth factors and integrin stimuli as well as intracellular protein scaffolds. In the present study, we investigated the role of Kinase suppressor of Ras (KSR), a scaffold that appears to regulate both Ras-Erk and Ras-PI3-K activity in influencing mast cell function. In vivo, KSR−/− mice have a 2–3 fold reduction of resident mast cells in multiple organs including the peritoneum and the skin as evaluated by scoring Alcian blue positive cells. To evaluate the mechanistic underpinnings of these in vivo observations, bone marrow derived mast cells (BMMCs) were generated and proliferation, survival, degranulation, and migration was examined. A 3–4 fold reduction in kit-ligand mediated proliferation as measured by [3H]thymidine incorporation was observed in KSR−/− BMMCs as compared to WT BMMCs. In addition, a 50% increase in apoptosis was observed in KSR−/− mast cells as compared to that in WT cells as measured by flow cytometeric analysis using Annexin/PI staining. Given that Erk and Akt are established molecular targets control proliferation and survival, respectively; we next performed western blots to evaluate if the changes in biological activity was associated with these signaling pathways. Importantly, a reduction in phosphorylation of ERK and phosphorylation of AKT was observed in the KSR −/− BMMCs as compared to that in WT BMMCs. Given the role of PI3-K signals in mediating cytoskeletal organization in mast cells, we next tested whether the reduction in PI3-K signals was associated with a reduction in degranulation and migration. Following stimulation with kit-ligand and cross-linking of the IgE receptor, KSR−/− mast cells were found to have a 30–50% decrease in b-hexosaminidase release. Moreover, KSR−/− mast cells have up to a 5 fold reduction in migration to kit-ligand as measured over a range of kit-ligand concentrations. Collectively, the in vivo and in vitro studies suggest that KSR is an important regulatory kinase that may be a viable molecular target for modulating inflammatory mast cell functions.

Dexamethasone and CD300a activation display additive inhibitory effect on human and murine mast cell functions

2021 ◽  
Author(s):  
Pratibha Gaur ◽  
Fidan Rahimli Alekberli ◽  
Laila Karra ◽  
David Mankuta ◽  
Micha Ben Zimra ◽  
...  
Keyword(s):  
Mast Cell ◽  
Inhibitory Effect ◽  
Cell Functions ◽  
Murine Mast Cell

Negative signals from FcεRI engagement attenuate mast cell functions

2007 ◽  
Vol 55 (4) ◽  
pp. 219-229 ◽  
Author(s):  
Rosa Molfetta ◽  
Giovanna Peruzzi ◽  
Angela Santoni ◽  
Rossella Paolini
Keyword(s):  
Mast Cell ◽  
Cell Functions

scholarly journals Strain difference of murine bone marrow-derived mast cell functions

2005 ◽  
Vol 78 (3) ◽  
pp. 605-611 ◽  
Author(s):  
Junko Noguchi ◽  
Etsushi Kuroda ◽  
Uki Yamashita
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Strain Difference ◽  
Murine Bone Marrow ◽  
Cell Functions

The Role of Proopiomelanocortin-Derived Peptides in Skin Fibroblast and Mast Cell Functions

2006 ◽  
Vol 885 (1) ◽  
pp. 268-276 ◽  
Author(s):  
PATRIZIA TEOFOLI ◽  
ALESSANDRA FREZZOLINI ◽  
PIETRO PUDDU ◽  
ORNELLA PITÀ ◽  
ALAIN MAUVIEL ◽  
...  
Keyword(s):  
Mast Cell ◽  
Skin Fibroblast ◽  
Cell Functions

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.

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 Fine-tuning Mast Cells is Essential for the Maintenance and Regulation of the Systemic and Immune Homeostasis

2021 ◽  
Vol 10 (2) ◽  
pp. 60
Author(s):  
Sylvia Frisancho-Kiss
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Scientific Literature ◽  
Fine Tuning ◽  
Viral Reservoir ◽  
Evolutionary Perspective ◽  
Cell Functions ◽  
The Past ◽  
Allergies And Asthma

During the past decades, populous expansion in mast cell scientific literature came forth with more, than forty-four thousand PubMed publications available to date. Such surge is due to the appreciation of the momentous role of mast cells in the evolution of species, in the development and maintenance of vital physiological functions, such as reproduction, homeostasis, and fluids, diverse immunological roles, and the potential of far-reaching effects despite minute numbers. While the emerging knowledge of the importance of mast cells in equilibrium comes of age when looking at the matter from an evolutionary perspective, the recognition of mast cells beyond detrimental performance in allergies and asthma, during protection against parasites, falters. Beyond well known classical functions, mast cells can process and present antigens,can serve as a viral reservoir, can respond to hormones and xenobiotics,initiate antiviral and antibacterial responses, phagocytosis, apoptosis, and participate in important developmental cornerstones. During evolution,upon the development of a sophisticated niche of innate and adaptive cell populations, certain mast cell functions became partially transmutable,yet the potency of mast cells remained considerable. Reviewing mast cells enables us to reflect on the certitude, that our sophisticated, complex physiology is rooted deeply in evolution, which we carry ancient remnants of, ones that may have decisive roles in our functioning. This communication sets out the goal of characterizing mast cells, particularly the aspects less in limelight yet of immense significance, without the aspiration exhaust it all.

scholarly journals The rat c-kit ligand, stem cell factor, induces c-kit receptor-dependent mouse mast cell activation in vivo. Evidence that signaling through the c-kit receptor can induce expression of cellular function.

1992 ◽  
Vol 175 (1) ◽  
pp. 245-255 ◽  
Author(s):  
B K Wershil ◽  
M Tsai ◽  
E N Geissler ◽  
K M Zsebo ◽  
S J Galli
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Tyrosine Kinase Receptor ◽  
Kit Ligand ◽  
Kit Receptor

Interactions between products of the mouse W locus, which encodes the c-kit tyrosine kinase receptor, and the Sl locus, which encodes a ligand for c-kit receptor, which we have designated stem cell factor (SCF), have a critical role in the development of mast cells. Mice homozygous for mutations at either locus exhibit several phenotypic abnormalities including a virtual absence of mast cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation of normal mast cells in vitro or in vivo, and also can result in repair of the mast cell deficiency of Sl/Sld mice in vivo. We now report that administration of SCF intradermally in vivo results in dermal mast cell activation and a mast cell-dependent acute inflammatory response. This effect is c-kit receptor dependent, in that it is not observed when SCF is administered to mice containing dermal mast cells expressing functionally inactive c-kit receptors, is observed with both glycosylated and nonglycosylated forms of SCF, and occurs at doses of SCF at least 10-fold lower on a molar basis than the minimally effective dose of the classical dermal mast cell-activating agent substance P. These findings represent the first demonstration in vivo that a c-kit ligand can result in the functional activation of any cellular lineage expressing the c-kit receptor, and suggest that interactions between the c-kit receptor and its ligand may influence mast cell biology through complex effects on proliferation, maturation, and function.

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