Recombinant stem cell factor-induced mast cell activation and smooth muscle contraction in human bronchi.

1994 ◽  
Vol 11 (6) ◽  
pp. 646-650 ◽  
Author(s):  
B J Undem ◽  
L M Lichtenstein ◽  
W C Hubbard ◽  
S Meeker ◽  
J L Ellis
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Muscle Contraction ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
Smooth Muscle Contraction ◽  
Mast Cell Activation ◽  
Human Bronchi

Effects of a selection of histone deacetylase inhibitors on mast cell activation and airway and colonic smooth muscle contraction

2008 ◽  
Vol 8 (13-14) ◽  
pp. 1793-1801 ◽  
Author(s):  
El-Sayed K Assem ◽  
Kheng H Peh ◽  
Beatrice Y C Wan ◽  
Brian J Middleton ◽  
Jon Dines ◽  
...  
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Histone Deacetylase ◽  
Cell Activation ◽  
Histone Deacetylase Inhibitors ◽  
Smooth Muscle Contraction ◽  
Mast Cell Activation ◽  
Selection Of

scholarly journals Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction

2021 ◽  
Author(s):  
Goutham Pattabiraman ◽  
Ashlee J Bell-Cohn ◽  
Stephen F. Murphy ◽  
Daniel J Mazur ◽  
Anthony J Schaeffer ◽  
...  
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Mast Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Critical Role ◽  
Smooth Muscle Contraction ◽  
Urinary Dysfunction ◽  
Mast Cell Activation ◽  
Prostate Inflammation

Intraurethral inoculation of mice with uropathogenic E. coli (CP1) results in prostate inflammation, fibrosis, and urinary dysfunction, recapitulating some but not all of the pathognomonic clinical features associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). In both patients with LUTS and in CP1-infected mice, we observed increased numbers and activation of mast cells and elevated levels of prostate fibrosis. Therapeutic inhibition of mast cells using a combination of mast cell stabilizer (MCS), cromolyn sodium, and the histamine 1 receptor antagonist (H1RA), cetirizine di-hydrochloride, in the mouse model resulted in reduced mast cell activation in the prostate and significant alleviation of urinary dysfunction. Treated mice showed reduced prostate fibrosis, less infiltration of immune cells, and decreased inflammation. In addition, as opposed to symptomatic CP1-infected mice, treated mice showed reduced myosin light chain (MLC)-2 phosphorylation, a marker of prostate smooth muscle contraction. These results show that mast cells play a critical role in the pathophysiology of urinary dysfunction and may be an important therapeutic target for men with BPH/LUTS.

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.

Mast Cell Effects on Esophageal Smooth Muscle and their Potential Role in Eosinophilic Esophagitis and Achalasia

2020 ◽  
Author(s):  
Melissa R Nelson ◽  
Xi Zhang ◽  
Zui Pan ◽  
Stuart Jon Spechler ◽  
Rhonda F. Souza
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Mast Cells ◽  
Muscle Contraction ◽  
Eosinophilic Esophagitis ◽  
Muscularis Propria ◽  
Smooth Muscle Contraction ◽  
Enteric Neurons ◽  
Mast Cell Activation ◽  
Parkinson’S Diseases

Mast cells and eosinophils are the key effector cells of allergic disorders. Although most studies on eosinophilic esophagitis (EoE), an allergic disorder of the esophagus, have focused on the role of eosinophils, recent studies suggest a major role for mast cells in causing the clinical manifestations of this disease. Cellular and animal studies have demonstrated that mast cells can cause esophageal muscle cells to proliferate and differentiate into a more contractile phenotype, and that mediators released by degranulating mast cells such as tryptase and histamine can activate smooth muscle contraction pathways. Thus, activated mast cells in the esophageal muscularis propria might cause esophageal motility abnormalities, including the failure of lower esophageal sphincter relaxation typical of achalasia. In addition, mast cells have been implicated in the pathogenesis of a number of neurodegenerative disorders of the central nervous system such as Alzheimer's and Parkinson's diseases, because degranulating mast cells release pro-inflammatory and cytotoxic mediators capable of damaging neurons. Such mast cell degranulation in the myenteric plexus of the esophagus could cause the loss of enteric neurons that characterizes achalasia. In this report, we review the molecular mechanisms of esophageal smooth muscle contraction, and how mast cells products might affect that muscle and cause neurodegeneration in the esophagus. Based on these data, we present our novel, conceptual model for an allergy-induced form of achalasia mediated by mast cell activation in the esophageal muscularis propria.

Abstract 15720: Transmembrane Stem Cell Factor Delivered in Nanocarriers Promotes Angiogenesis in Ischemia Without Mast Cell Activation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Eri Takematsu ◽  
Sanjana Srinath ◽  
Michael Sherman ◽  
Andrew K Dunn ◽  
Aaron Baker
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
The Body ◽  
Mast Cell Activation ◽  
Protein Therapy ◽  
Current Standard ◽  
Therapeutic Benefits

Introduction: The current standard cares for peripheral artery disease (PAD) include surgical revascularizations with bypass grafting or percutaneous interventions. However, these interventions cannot be performed in a significant portion of patients, and many do not respond to these surgical procedures. Protein therapy to stimulate the body to create new vasculature is another alternative, which is minimally invasive to patients. Stem cell factor (SCF) is a candidate protein for treating PAD, but clinical use of SCF has been limited due to toxicity related to mast cell activation. SCF also exists in a transmembrane form (tmSCF), possessing differential activities from soluble SCF and has not been explored as a therapeutic agent. Results: To develop tmSCF as a therapeutic we created tmSCF embedded in liposome or lipid nanodisc (Fig. A) . Hindlimb ischemia model on WT and ob/ob mice showed that tmSCF proteliposome (tmSCFPL) and nanodisc (tmSCFND) improved blood flow recovery significantly more than control (Fig. B, C) . Mouse model of anaphylaxis revealed that tmSCF-based therapies did not activate mast cells (Fig. D, E) . Colocalization assay of c-Kit and clathrin/caveolin revealed that mast cells preferentially use clathrin-mediated pathways to internalize SCF and caveolin-mediated pathways for tmSCF-based therapies (Fig. F, G) . Surface c-Kit internalization study on mast cells showed faster uptake of SCF in comparison to tmSCF-based therapies (Fig. H) . Previous study indicates that clathrin-mediated internalization causes increased activation of mast cells. Our studies together with the previous finding suggest that mast cell activation does not occur for tmSCF-based therapies because of the slower uptake, greater utilization of the caveolin internalization pathway and weaker activation of mast cells. Conclusions: TmSCF-based therapies can provide therapeutic benefits without off-target effects on mast cells by tuning activation with nanocarriers.

scholarly journals Stem Cell Factor Programs the Mast Cell Activation Phenotype

2012 ◽  
Vol 188 (11) ◽  
pp. 5428-5437 ◽  
Author(s):  
Tomonobu Ito ◽  
Daniel Smrž ◽  
Mi-Yeon Jung ◽  
Geethani Bandara ◽  
Avanti Desai ◽  
...  
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
Mast Cell Activation

gp49B1 suppresses stem cell factor-induced mast cell activation-secretion and attendant inflammation in vivo

2003 ◽  
Vol 33 (8) ◽  
pp. 2262-2268 ◽  
Author(s):  
Anna M. Feldweg ◽  
Daniel S. Friend ◽  
Joseph S. Zhou ◽  
Yoshihide Kanaoka ◽  
Massoud Daheshia ◽  
...  
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
Mast Cell Activation

scholarly journals Transmembrane Stem Cell Factor Protein Therapeutics Enhance Revascularization in Ischemia without Mast Cell Activation

2020 ◽  
Author(s):  
Eri Takematsu ◽  
Jeff Auster ◽  
Po-Chih Chen ◽  
Sanjana Srinath ◽  
Sophia Canga ◽  
...  
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Dependent Manner ◽  
Therapeutic Benefits ◽  
A Cell ◽  
Cell Mobilization ◽  
Lipid Nanodiscs

AbstractStem cell factor (SCF) is a cytokine that regulates hematopoiesis and other biological processes. While clinical treatments using SCF would be highly beneficial, these have been limited by toxicity related to mast cell activation. Transmembrane SCF (tmSCF) has differential activity from soluble SCF and has not been explored as a therapeutic agent. We created novel therapeutics using tmSCF embedded in proteoliposomes or lipid nanodiscs. Mouse models of anaphylaxis and ischemia revealed the tmSCF-based therapies did not activate mast cells and improved the revascularization in the ischemic hind limb. Proteoliposomal tmSCF preferentially acted on endothelial cells to induce angiogenesis while tmSCF nanodiscs had greater activity in inducing stem cell mobilization and recruitment to the site of injury. The type of lipid nanocarrier used altered the relative cellular uptake pathways and signaling in a cell type dependent manner. Overall, we found that tmSCF-based therapies can provide therapeutic benefits without off target effects.

scholarly journals Calcineurin–Rcan1 Interaction Contributes to Stem Cell Factor–Mediated Mast Cell Activation

2013 ◽  
Vol 191 (12) ◽  
pp. 5885-5894 ◽  
Author(s):  
Zhengli Wu ◽  
Yanhong Li ◽  
Adam J. MacNeil ◽  
Robert D. Junkins ◽  
Jason N. Berman ◽  
...  
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
Mast Cell Activation

scholarly journals Novel airway smooth muscle–mast cell interactions and a role for the TRPV4-ATP axis in non-atopic asthma

2020 ◽  
Vol 56 (1) ◽  
pp. 1901458 ◽  
Author(s):  
Sara J. Bonvini ◽  
Mark A. Birrell ◽  
Eric Dubuis ◽  
John J. Adcock ◽  
Michael A. Wortley ◽  
...  
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Mast Cells ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Cell Activation ◽  
Transient Receptor Potential ◽  
Atopic Asthma ◽  
Mast Cell Activation ◽  
Tracheal Tissue

Mast cell–airway smooth muscle (ASM) interactions play a major role in the immunoglobulin (Ig)E- dependent bronchoconstriction seen in asthma but less is known about IgE-independent mechanisms of mast cell activation. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) activation causes contraction of human ASM via the release of cysteinyl leukotrienes (cysLTs) but the mechanism is unknown. The objective of the present study was to investigate a role for IgE-independent, mast cell–ASM interaction in TRPV4-induced bronchospasm.Bronchoconstriction was measured in anaesthetised guinea pigs and contraction of human and guinea-pig airway tissue assessed using isometric tension measurements. Increases in intracellular [Ca2+] were imaged using the Ca2+-sensitive dye FURA2, and time-lapse ptychography was utilised as a surrogate for contraction of ASM cells.The TRPV4 agonist GSK1016790A caused contraction in vivo in the guinea pig, and in human and guinea-pig tracheal tissue, which was inhibited by the TRPV4 antagonist GSK2193874. GSK1016790A increased [Ca2+]i and released ATP in human ASM cells without causing contraction. TRPV4 and ATP evoked contraction in isolated tracheal tissue but co-culture experiments indicated a requirement for human lung mast cells. Expression profiling and pharmacological studies demonstrated that mast cell activation was dependent upon ATP activating the P2X4 receptor. Trypsin was shown to evoke contraction of tracheal tissue via activation of PAR-2-TRPV4-ATP-cysLT axis indicating the potential disease relevance of this signalling pathway.TRPV4 activation increases [Ca2+]i and releases ATP from ASM cells triggering P2X4-dependent release of cysLTs from mast cells resulting in ASM contraction. This study delineates a novel mast cell–ASM interaction and TRPV4 as a driver of IgE-independent mast cell-dependent bronchospasm.

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