scholarly journals Induction of Mast-Cell Accumulation by Promutoxin, an Arg-49 PhospholipaseA2

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Ji-Fu Wei ◽  
Xiao-Long Wei ◽  
Ya-Zhen Mo ◽  
Haiwei Yang ◽  
Shaoheng He
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Adhesion Molecules ◽  
Snake Venom ◽  
Platelet Activating Factor ◽  
Fold Increase ◽  
Inflammatory Cells ◽  
Cell Accumulation ◽  
Snake Venom Phospholipase ◽  
Main Component

Local inflammation is a prominent characteristic of snakebite wound, and snake-venom phospholipase A2s (PLA2s) are some of the main component that contribute to accumulation of inflammatory cells. However, the action of an R49 PLA2s, promutoxin fromProtobothrops mucrosquamatusvenom, on mast-cell accumulation has not been previously examined. Using a mouse peritoneal model, we found that promutoxin can induce approximately-6-fold increase in mast-cell accumulation, and the response lasts at least for 16 h. The promutoxin-induced mast cell accumulation was inhibited by cyproheptadine, terfenadine, and Ginkgolide B, indicating that histamine and platelet-activating factor (PAF) is likely to contribute to the mast-cells accumulation. Preinjection of antibodies against adhesion molecules ICAM-1, CD18, CD11a, and L-selectin showed that ICAM-1, and CD18, CD11a are key adhesion molecules of promutoxin-induced mast-cell accumulation. In conclusion, promutoxin can induce accumulation of mast cells, which may contribute to snake-venom wound.

scholarly journals Induction of Mast Cell Accumulation by Tryptase via a Protease Activated Receptor-2 and ICAM-1 Dependent Mechanism

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xin Liu ◽  
Junling Wang ◽  
Huiyun Zhang ◽  
Mengmeng Zhan ◽  
Hanqiu Chen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Allergic Inflammation ◽  
Fold Increase ◽  
Secretory Product ◽  
Effector Cells ◽  
Migration Assay ◽  
Cell Accumulation ◽  
Model Cell

Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection. Inhibitors of tryptase, an antagonist of PAR-2 FSLLRY-NH2, and pretreatment of mice with anti-ICAM-1, anti-CD11a, and anti-CD18 antibodies dramatically diminished tryptase induced mast cell accumulation. On the other hand, PAR-2 agonist peptides SLIGRL-NH2and tc-LIGRLO-NH2provoked mast cell accumulation following injection. These implicate that tryptase induced mast cell accumulation is dependent on its enzymatic activity, activation of PAR-2, and interaction between ICAM-1 and LFA-1. Moreover, induction of trans-endothelium migration of mast cellsin vitroindicates that tryptase acts as a chemoattractant. In conclusion, provocation of mast cell accumulation by mast cell tryptase suggests a novel self-amplification mechanism of mast cell accumulation. Mast cell stabilizers as well as PAR-2 antagonist agents may be useful for treatment of allergic reactions.

Effects of Skin Mast Cells on Bleeding Time and Coagulation Activation at the Site of Platelet Plug Formation

1998 ◽  
Vol 79 (04) ◽  
pp. 843-847 ◽  
Author(s):  
Petteri Kauhanen ◽  
Petri Kovanen ◽  
Timo Reunala ◽  
Riitta Lassila
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Thrombin Generation ◽  
Bleeding Time ◽  
Normal Skin ◽  
Urticaria Pigmentosa ◽  
Primary Hemostasis ◽  
Cell Accumulation ◽  
The Mean ◽  
Cutaneous Mast Cell

SummaryWe studied the effects of stimulated skin mast cells on bleeding time and thrombin generation which was measured using prothrombin fragment F 1+2 (F 1+2) and thrombin-antithrombin-III-complex (TAT). In 10 patients with urticaria pigmentosa (chronic cutaneous mast cell accumulation) the mean bleeding time was significantly prolonged in wounds made on urticaria pigmentosa lesions vs. normal skin (460 ± 34 vs. 342 ± 27 s, p = 0.005). In 10 atopic subjects skin incisions were made on prick-tested sites 30, 60, 120 and 240 min after administration of an allergen (acute mast cell stimulation), histamine or vehicle. The mean bleeding time was significantly prolonged at all time points, being maximal at 120 min (60% prolonged) in wounds made on allergen-stimulated skin areas (p <0.01) compared with histamine or vehicle sites. Administration of allergen or histamine lowered the TAT concentration in the bleeding-time blood. Furthermore, TAT and F 1+2 levels in the bleeding-time blood were lower at 60, 120 and 240 min after allergen or histamine application in comparison with samples collected at 30 min. We conclude that skin mast cells can regulate primary hemostasis by prolonging bleeding time and by inhibiting thrombin generation.

scholarly journals Pathogenic role of mast cells in experimental eosinophilic esophagitis

2013 ◽  
Vol 304 (12) ◽  
pp. G1087-G1094 ◽  
Author(s):  
Rituraj Niranjan ◽  
Parm Mavi ◽  
Madhavi Rayapudi ◽  
Scott Dynda ◽  
Anil Mishra
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Muscle Cell ◽  
Significant Role ◽  
Eosinophilic Esophagitis ◽  
Brdu Incorporation ◽  
Dependent Manner ◽  
Wild Type ◽  
Cell Hyperplasia ◽  
Cell Accumulation

Eosinophilic esophagitis (EoE) is a chronic allergic disease characterized by esophageal intraepithelial eosinophils, extracellular eosinophil granule deposition, induced mast cell accumulation, and epithelial cell hyperplasia. However, the processes involved in the development of a number of these characteristics are largely unknown. Herein, we tested the hypothesis whether induced mast cell accumulation in the esophagus has a role in promoting EoE pathogenesis. Accordingly, we induced experimental EoE in wild-type mice, mast cell-deficient WWv mice, and mast cell-reconstituted WWv mice. We report that esophageal mast cell numbers increase in parallel with eosinophils in a dose- and time-dependent manner following the induction of allergen-induced EoE. The induced mast cells are localized in the esophageal lamina propria and muscular mucosa but have no influence on promoting esophageal eosinophilia. The 5′-bromodeoxyuridine (BrdU) incorporation analysis indicated that mast cells have a significant role in muscle cell hyperplasia and hypertrophy. In addition, the wild-type and mast cell-reconstituted WWv mice showed a comparable number of BrdU+ cells in the esophageal muscular mucosa following allergen-induced EoE. In conclusion, we provide for the first time direct evidence that mast cell promotes muscle cell hyperplasia and hypertrophy and may have a significant role in promoting esophageal functional abnormalities in EoE.

scholarly journals Enhanced mucosal permeability and nitric oxide synthase activity in jejunum of mast cell deficient mice

Gut ◽  
1997 ◽  
Vol 41 (5) ◽  
pp. 636-641 ◽  
Author(s):  
S Komatsu ◽  
M B Grisham ◽  
J M Russell ◽  
D N Granger
Keyword(s):  
Nitric Oxide ◽  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Cells ◽  
Inhibitory Influence ◽  
Mucosal Permeability ◽  
Nos Inhibitor ◽  
Plasma Nitrate ◽  
Oxide Synthase ◽  
Inducible Nos

Background—Recent reports have described a modulating influence of nitric oxide (NO) on intestinal mucosal permeability and have implicated a role for mast cells in this NO mediated process.Aims—To assess further the contribution of mast cells to the mucosal permeability changes elicited by the NO synthase (NOS) inhibitor NG-nitro-l-arginine methylester (l-NAME), using mast cell deficient (W/WV) and mast cell replete mice (+/+).Methods—Chromium-51 EDTA clearance (from blood to jejunal lumen), jejunal NOS and myeloperoxidase (MPO) activities, and plasma nitrate/nitrite levels were monitored.Results—The increased EDTA clearance elicited by intraluminal l-NAME in W/WV mice (4.4-fold) was significantly greater than the response observed in control (+/+) mice (1.8-fold). The exacerbated response in W/Wv mice was greatly attenuated by pretreatment with either dexamethasone (1.3-fold) or the selective inducible NOS inhibitor, aminoguanidine (1.4-fold), and partially attenuated by the mast cell stabiliser, lodoxamide (2.9-fold). Jejunal inducible NOS activity was significantly higher in W/WV than in +/+ mice, while jejunal MPO was lower in W/WV mice than in +/+ mice, suggesting that the higher inducible NOS in W/WV does not result from the recruitment of inflammatory cells into the gut. The higher inducible NOS activity in the jejunum of W/WV was significantly reduced by dexamethasone treatment.Conclusions—Our results suggest that mast cells normally serve to inhibit inducible NOS activity tonically in the gut and that inhibitors of NOS elicit a larger permeability response when this tonic inhibitory influence is released by mast cell depletion.

scholarly journals Molecular mechanism of mast cell–mediated innate defense against endothelin and snake venom sarafotoxin

2007 ◽  
Vol 204 (11) ◽  
pp. 2629-2639 ◽  
Author(s):  
Lars A. Schneider ◽  
Susan M. Schlenner ◽  
Thorsten B. Feyerabend ◽  
Markus Wunderlin ◽  
Hans-Reimer Rodewald
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Molecular Mechanism ◽  
Snake Venom ◽  
Single Amino Acid ◽  
Peptide Substrates ◽  
Innate Defense ◽  
Cell Enzyme ◽  
Peptide Family ◽  
Single Protease

Mast cells are protective against snake venom sarafotoxins that belong to the endothelin (ET) peptide family. The molecular mechanism underlying this recently recognized innate defense pathway is unknown, but secretory granule proteases have been invoked. To specifically disrupt a single protease function without affecting expression of other proteases, we have generated a mouse mutant selectively lacking mast cell carboxypeptidase A (Mc-cpa) activity. Using this mutant, we have now identified Mc-cpa as the essential protective mast cell enzyme. Mass spectrometry of peptide substrates after cleavage by normal or mutant mast cells showed that removal of a single amino acid, the C-terminal tryptophan, from ET and sarafotoxin by Mc-cpa is the principle molecular mechanism underlying this very rapid mast cell response. Mast cell proteases can also cleave ET and sarafotoxin internally, but such “nicking” is not protective because intramolecular disulfide bridges maintain peptide function. We conclude that mast cells attack ET and sarafotoxin exactly at the structure required for toxicity, and hence sarafotoxins could not “evade” Mc-cpa's substrate specificity without loss of toxicity.

scholarly journals Elevated Plasma Level of Interferon-λ1 in Chronic Spontaneous Urticaria: Upregulated Expression in CD8+and Epithelial Cells and Induction of Inflammatory Cell Accumulation

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
S. F. Wang ◽  
X. Q. Gao ◽  
Y. N. Xu ◽  
D. N. Li ◽  
H. Y. Wang ◽  
...  
Keyword(s):  
Mast Cells ◽  
Inflammatory Cell ◽  
Inflammatory Cells ◽  
Chronic Spontaneous Urticaria ◽  
Intercellular Adhesion Molecule ◽  
Double Labeling ◽  
Cell Accumulation ◽  
Healthy Control ◽  
Dose Dependent Increase ◽  
Dose Dependent

Interferon- (IFN-)λ1 is regarded as a potent bio-active molecule in innate immunity. However, little is known about its role in chronic spontaneous urticaria (CSU). We therefore investigated expression of IFN-λ1 in CSU, its cellular location, and its influence on inflammatory cell accumulation by using flow cytometry analysis, skin tissue dispersion, immunohistochemical stain, and a mouse peritoneal inflammation model. The results showed that level of IFN-λ1 was 2.0-fold higher in plasma of the patients with CSU than the level in healthy control (HC) subjects. Among leukocytes examined, only CD8+T cells expressed more IFN-λ1 in CSU blood. Double labeling immunohistochemical staining revealed that IFN-λ1+inflammatory cells such as mast cells, eosinophils, B cells, neutrophils, and macrophages were mainly located in dermis, whereas epidermis tissue highly expressed IFN-λ1. IFN-λ1 induced a dose-dependent increase in number of eosinophils, lymphocytes, mast cells, macrophages, and neutrophils in the peritoneum of mice at 6 h following injection, which was inhibited by pretreatment of the animals with anti-intercellular adhesion molecule- (ICAM-) 1 and/or anti-L-selectin antibodies. In conclusion, IFN-λ1 is likely to play a role in the pathogenesis of CSU. Blocking IFN-λ1 production may help to reduce the accumulation of inflammatory cells in the involved CSU skin.

Abstract 476: Mast Cell--Mediated Neutrophil Influx Enhances Plaque Progression

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Anouk Wezel ◽  
H Maxime Lagraauw ◽  
Daniël van der Velden ◽  
Saskia C de Jager ◽  
Paul H Quax ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Neutrophil Migration ◽  
Fold Increase ◽  
Mast Cell Activation ◽  
Neutrophil Influx ◽  
Migration Assay ◽  
Cell Activator

Rationale: Activated mast cells have been identified in atherosclerotic plaques. As mast cells have the ability to release chemokines that mediate leukocyte fluxes, we propose that activated mast cells play a pivotal role in leukocyte recruitment during atherosclerosis. Methods and Results: Diet fed B-cell deficient apoE-/-muChain mice, which lack endogenous IgE, received 6 IgE or PBS injections over a period of 8 weeks. Mast cells in the aortic root were significantly more activated after IgE treatment and concomitantly, we detected an increase in plaque size (P=0.050). Intriguingly, a striking increase in the amount of perivascular neutrophils was observed in IgE treated mice (control: 57.6 ± 10.6 neutrophils/mm2 tissue; IgE: 183.0 ± 38.7 neutrophils/mm2 tissue; P=0.01). In order to investigate if activated mast cells can directly attract neutrophils, we injected C57Bl/6 or mast cell deficient Kit(W-sh/W-sh) mice intra-peritoneal with the mast cell activator 48/80. Interestingly, mast cell activation led to a massive neutrophil influx into the peritoneal cavity, while neutrophil numbers in mast cell deficient mice remained unaffected. To confirm these findings, we performed an in vitro migration assay. Indeed, supernatant of activated mast cells caused a 3-fold increase in neutrophil migration (P=0.007). Moreover, addition of anti-CXCR2 to the neutrophils resulted in a major reduction of migration (P=0.03) whereas anti-CXCR4 did not reduce migration significantly. Conclusions: Chemokines released from activated perivascular mast cells induce neutrophil recruitment to the atherosclerotic plaque, thereby aggravating the inflammatory response.

scholarly journals Immunoglobulin E–dependent Active Fatal Anaphylaxis in Mast Cell–deficient Mice

1998 ◽  
Vol 188 (9) ◽  
pp. 1587-1592 ◽  
Author(s):  
Il Hwan Choi ◽  
Young Min Shin ◽  
Jae Seung Park ◽  
Moo Sam Lee ◽  
Eue Hyeog Han ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Platelet Activating Factor ◽  
Serum Levels ◽  
Effector Cells ◽  
Plasma Histamine Level ◽  
Central Effector ◽  
Fatal Anaphylaxis

Mast cells have long been believed to be the central effector cells in the development of immunoglobulin (Ig)E-dependent anaphylaxis. In this study, we investigated the role of mast cells in IgE-dependent hapten-induced active fatal anaphylaxis using mast cell–deficient WBB6F1- W/Wv (W/Wv) and congenic normal (+/+) mice. Although a 5-min delay in shock signs and death were observed in W/Wv mice, 100% fatal reactions to penicillin V (Pen V) occurred in both +/+ and W/Wv mice. Administration of monoclonal anti–IL-4 antibody completely prevented the fatal reactions, and the effect of anti–IL-4 was associated with its suppressive activity on Pen V–specific serum levels of IgE, but not IgG. The platelet-activating factor (PAF) antagonist, BN 50739, completely prevented the fatal reactions in both strains of mice. Our kinetic study revealed, in contrast to no elevation of plasma histamine level in W/Wv mice, high levels of PAF in the circulation after challenge in both +/+ and W/Wv mice, albeit to a lesser degree in the latter case. These data indicate that cells other than mast cells are sufficient to induce an IgE-dependent active fatal anaphylaxis by elaborating PAF, which is the critical mediator for fatal murine anaphylaxis.

scholarly journals Establishment in culture and characterization of a strain with mast cell and monocytic properties from the bone marrow of a child with diffuse cutaneous mastocytosis

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 290-303 ◽  
Author(s):  
SA Krilis ◽  
SG Warneford ◽  
J Macpherson ◽  
S Kyradji ◽  
L Dalla-Pozza ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Platelet Activating Factor ◽  
Prostaglandin D2 ◽  
Adherent Cells ◽  
Phenotypic Features ◽  
Nonadherent Cells

Abstract Bone marrow was isolated from a child with congenital mastocytosis. Upon prolonged in vitro culture, initially in the presence of interleukin-3 (IL-3), a population of relatively large fusiform, strongly adherent cells grew out plus a subpopulation of smaller nonadherent cells. The morphology of the adherent cells was not typical of fibroblasts, epithelial cells, nor of standard hematopoietic cell types, whereas the morphology of the nonadherent cells resembled mast cells. Neither cell type required the presence of IL-3 nor a feeder layer of fibroblasts for continued growth. Attempts to isolate the two populations were unsuccessful. This cell strain comprised of both cell populations has been termed human bone marrow-derived mastocytosis cells (HBM-M). These cells were found to possess some of the cytochemical, ultrastructural, and surface phenotypic features of degranulated mast cells. They reacted with the mast cell marker, monoclonal antibody YB5.B8, but not with the basophil specific monoclonal antibody Bsp-1 and released the inflammatory mediators histamine, leukotriene C4, prostaglandin D2, and platelet-activating factor constitutively. This release was not potentiated by immunologic- or nonimmunologic-activating stimuli. In addition, they exhibited cytochemical and surface phenotypic features of monocytes. Our results indicate that a population of abnormal proliferative cells exist in the marrow of this patient; that these cells may be responsible for the patient's pronounced systemic proliferation of mast cells and the associated symptoms; and that the cell's mast cell, monocyte properties may be indicative of a common bone marrow-derived mast cell/monocyte precursor.

scholarly journals Establishment and Characterization of a Murine Mucosal Mast Cell Culture Model

2019 ◽  
Author(s):  
Aya Kakinoki ◽  
Tsuyoshi Kameo ◽  
Shoko Yamashita ◽  
Kazuyuki Furuta ◽  
Satoshi Tanaka
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Responses ◽  
Mucosal Mast Cell ◽  
Cell Accumulation ◽  
Culture Model ◽  
Ige Mediated ◽  
Interleukin 9 ◽  
Mast Cell Culture

Accumulating evidence suggests that mast cells should play critical roles in disruption and maintenance of intestinal homeostasis, although it remains unknown how they affect local microenvironment. Interleukin-9 (IL-9) was found to play critical roles in intestinal mast cell accumulation induced in various pathological conditions, such as parasite infection and oral allergen-induced anaphylaxis. Newly recruited intestinal mast cells trigger inflammatory responses and damage epithelial integrity through release of a wide variety of mediators including mast cell proteases. We established a novel culture model (mucosal mast cell-like cultured mast cells, MMC-like MCs), in which murine IL-3-dependent bone marrow-derived cultured mast cells (BMMCs) were further cultured in the presence of stem cell factor and IL-9. In MMC-like MCs, drastic up-regulation of Mcpt1 and Mcpt2 was found. Although histamine storage and tryptase activity were significantly downregulated in the presence of SCF and IL-9, it was entirely reversed when mast cells were co-cultured with a murine fibroblastic cell line, Swiss 3T3. MMC-like MCs underwent degranulation upon IgE-mediated antigen stimulation, which was found to less sensitive to lower concentrations of IgE in comparison with BMMCs. This model might be useful for investigation of the spatiotemporal changes of newly recruited intestinal mast cells.

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