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.

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 Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice

Blood ◽  
2011 ◽  
Vol 118 (26) ◽  
pp. 6930-6938 ◽  
Author(s):  
Jennifer N. Lilla ◽  
Ching-Cheng Chen ◽  
Kaori Mukai ◽  
Maya J. BenBarak ◽  
Christopher B. Franco ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Genetic Manipulation ◽  
Allergic Inflammation ◽  
Myeloid Cell ◽  
Hematopoietic Cell ◽  
Cell Populations ◽  
And Function

Abstract It has been reported that the intracellular antiapoptotic factor myeloid cell leukemia sequence 1 (Mcl-1) is required for mast cell survival in vitro, and that genetic manipulation of Mcl-1 can be used to delete individual hematopoietic cell populations in vivo. In the present study, we report the generation of C57BL/6 mice in which Cre recombinase is expressed under the control of a segment of the carboxypeptidase A3 (Cpa3) promoter. C57BL/6-Cpa3-Cre; Mcl-1fl/fl mice are severely deficient in mast cells (92%-100% reduced in various tissues analyzed) and also have a marked deficiency in basophils (58%-78% reduced in the compartments analyzed), whereas the numbers of other hematopoietic cell populations exhibit little or no changes. Moreover, Cpa3-Cre; Mcl-1fl/fl mice exhibited marked reductions in the tissue swelling and leukocyte infiltration that are associated with both mast cell- and IgE-dependent passive cutaneous anaphylaxis (except at sites engrafted with in vitro–derived mast cells) and a basophil- and IgE-dependent model of chronic allergic inflammation, and do not develop IgE-dependent passive systemic anaphylaxis. Our findings support the conclusion that Mcl-1 is required for normal mast cell and basophil development/survival in vivo in mice, and also suggest that Cpa3-Cre; Mcl-1fl/fl mice may be useful in analyzing the roles of mast cells and basophils in health and disease.

scholarly journals Annexin A1 Mimetic Peptide Ac2-26 Modulates the Function of Murine Colonic and Human Mast Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Marcia Pereira Oliveira ◽  
Janesly Prates ◽  
Alexandre Dantas Gimenes ◽  
Silvia Graciela Correa ◽  
Sonia Maria Oliani
Keyword(s):  
Gastrointestinal Tract ◽  
Mast Cells ◽  
Allergic Inflammation ◽  
Bioactive Molecules ◽  
Human Mast Cell ◽  
Annexin A1 ◽  
Effector Cells ◽  
Formyl Peptide ◽  
Mast Cell Line

Mast cells (MCs) are main effector cells in allergic inflammation and after activation, they release stored (histamine, heparin, proteases) and newly synthesized (lipid mediators and cytokines) substances. In the gastrointestinal tract the largest MC population is located in the lamina propria and submucosa whereas several signals such as the cytokine IL-4, seem to increase the granule content and to stimulate a remarkable expansion of intestinal MCs. The broad range of MC-derived bioactive molecules may explain their involvement in many different allergic disorders of the gastrointestinal tract. Annexin A1 (AnxA1) is a 37 KDa glucocorticoid induced monomeric protein selectively distributed in certain tissues. Its activity can be reproduced by mimetic peptides of the N-terminal portion, such as Ac2-26, that share the same receptor FPR-L1. Although previous reports demonstrated that AnxA1 inhibits MC degranulation in murine models, the effects of exogenous peptide Ac2-26 on intestinal MCs or the biological functions of the Ac2-26/FPR2 system in human MCs have been poorly studied. To determine the effects of Ac2-26 on the function of MCs toward the possibility of AnxA1-based therapeutics, we treated WT and IL-4 knockout mice with peptide Ac2-26, and we examined the spontaneous and compound 48/80 stimulated colonic MC degranulation and cytokine production. Moreover, in vitro, using human mast cell line HMC-1 we demonstrated that exogenous AnxA1 peptide is capable of interfering with the HMC-1 degranulation in a direct pathway through formyl peptide receptors (FPRs). We envisage that our results can provide therapeutic strategies to reduce the release of MC mediators in inflammatory allergic processes.

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 Extracellular Vesicles as Emerging Players in Intercellular Communication: Relevance in Mast Cell-Mediated Pathophysiology

2021 ◽  
Vol 22 (17) ◽  
pp. 9176
Author(s):  
Irit Shefler ◽  
Pazit Salamon ◽  
Yoseph A. Mekori
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tumor Progression ◽  
Extracellular Vesicles ◽  
Allergic Inflammation ◽  
Specific Ige ◽  
Therapeutic Approaches ◽  
Effector Cells ◽  
High Affinity Receptor ◽  
Clinical Conditions

Mast cells are major effector cells in eliciting allergic responses. They also play a significant role in establishing innate and adaptive immune responses, as well as in modulating tumor growth. Mast cells can be activated upon engagement of the high-affinity receptor FcεRI with specific IgE to multivalent antigens or in response to several FcεRI-independent mechanisms. Upon stimulation, mast cells secrete various preformed and newly synthesized mediators. Emerging evidence indicates their ability to be a rich source of secreted extracellular vesicles (EVs), including exosomes and microvesicles, which convey biological functions. Mast cell-derived EVs can interact with and affect other cells located nearby or at distant sites and modulate inflammation, allergic response, and tumor progression. Mast cells are also affected by EVs derived from other cells in the immune system or in the tumor microenvironment, which may activate mast cells to release different mediators. In this review, we summarize the latest data regarding the ability of mast cells to release or respond to EVs and their role in allergic responses, inflammation, and tumor progression. Understanding the release, composition, and uptake of EVs by cells located near to or at sites distant from mast cells in a variety of clinical conditions, such as allergic inflammation, mastocytosis, and lung cancer will contribute to developing novel therapeutic approaches.

scholarly journals Critical role of P1-Runx1 in mouse basophil development

Blood ◽  
2012 ◽  
Vol 120 (1) ◽  
pp. 76-85 ◽  
Author(s):  
Kaori Mukai ◽  
Maya J. BenBarak ◽  
Masashi Tachibana ◽  
Keigo Nishida ◽  
Hajime Karasuyama ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mast Cell ◽  
Mast Cells ◽  
Critical Role ◽  
Allergic Inflammation ◽  
Normal Numbers ◽  
Related Transcription Factor ◽  
Distal Promoter

Abstract Runx1 P1N/P1N mice are deficient in the transcription factor distal promoter-derived Runt-related transcription factor 1 (P1-Runx1) and have a > 90% reduction in the numbers of basophils in the BM, spleen, and blood. In contrast, Runx1P1N/P1N mice have normal numbers of the other granulocytes (neutrophils and eosinophils). Although basophils and mast cells share some common features, Runx1P1N/P1N mice have normal numbers of mast cells in multiple tissues. Runx1P1N/P1N mice fail to develop a basophil-dependent reaction, IgE-mediated chronic allergic inflammation of the skin, but respond normally when tested for IgE- and mast cell–dependent passive cutaneous anaphylaxis in vivo or IgE-dependent mast cell degranulation in vitro. These results demonstrate that Runx1P1N/P1N mice exhibit markedly impaired function of basophils, but not mast cells. Infection with the parasite Strongyloides venezuelensis and injections of IL-3, each of which induces marked basophilia in wild-type mice, also induce modest expansions of the very small populations of basophils in Runx1P1N/P1N mice. Finally, Runx1P1N/P1N mice have normal numbers of the granulocyte progenitor cells, SN-Flk2+/−, which can give rise to all granulocytes, but exhibit a > 95% reduction in basophil progenitors. The results of the present study suggest that P1-Runx1 is critical for a stage of basophil development between SN-Flk2+/− cells and basophil progenitors.

Effect of Chicoric Acid on Mast Cell-Mediated Allergic Inflammation in Vitro and in Vivo

2015 ◽  
Vol 78 (12) ◽  
pp. 2956-2962 ◽  
Author(s):  
Na Young Lee ◽  
Kyung-Sook Chung ◽  
Jong Sik Jin ◽  
Keuk Soo Bang ◽  
Ye-Jin Eom ◽  
...  
Keyword(s):  
Mast Cell ◽  
Allergic Inflammation ◽  
Chicoric Acid

In-vitro and in-vivo Evaluation of Anti-asthmatic Activity of Eugenia jambolana bark

2021 ◽  
pp. 3337-3342
Author(s):  
Bhong Prabha N. ◽  
Naikawade Nilofar. S. ◽  
Mali Pratibha. R. ◽  
Bindu Madhavi. S.
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Animal Models ◽  
Aqueous Extract ◽  
Guinea Pigs ◽  
Bark Extract ◽  
Eugenia Jambolana ◽  
In Vivo Animal Models

Objectives: The present study designed to evaluate the Antiasthmatic activity of aqueous extract of bark of Eugenia Jambolana (AEEJ) on in vitro and in vivo animal models. Materials and methods: Different in vitro and in vivo animal models was used to study the anti asthmatic activity as isolated goat tracheal chain preparation, Acetylcholine and Histamine induced bronconstriction in guinea pigs, effect of drug extract on histamine release from mast cell was checked by clonidine-induced mast cell degranulation, and milk-induced eosinophilia and leukocytosis. Results: In-vitro study on goat tracheal chain preparation revealed that aqueous extract of Eugenia jambolana (AEEJ)bark exerted antagonistic effect on the histamine induced contraction. (P<0.05) The guinea pigs when exposed to 0.2% histamine aerosol showed signs of progressive dyspnoea leading to convulsions. AEEJ significantly prolonged the latent period of convulsions (PCT) as compared to control following the exposure of histamine (0.2%) aerosol (P<0.01). The observation of present study indicates aqueous extract of Eugenia jambolana shows significant inhibition of milk induced eosinophilia and leukocytosis. Group of animals pretreated with aqueous Eugenia jambolana bark extract showed significant reduction in degranulation of mast cells when challenged with clonidine. The prevention of degranulation process by the aqueous Eugenia jambolana bark extract (P<0.01) indicates a possible stabilizing effect on the mast cells, indicating mast cell stabilizing activity. Conclusions: Thus, AEEJ showed antihistaminic, mast cell stabilizing and protective in guinea pigs against histamine induced PCD, reduced eosinophilia and leukocytosis and hence possesses potential role in the treatment of asthma.

Development of hematopoietic cells lacking transcription factor GATA-1

Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 163-172 ◽  
Author(s):  
L. Pevny ◽  
C.S. Lin ◽  
V. D'Agati ◽  
M.C. Simon ◽  
S.H. Orkin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mast Cell ◽  
Cell Differentiation ◽  
Mast Cells ◽  
Blood Cell ◽  
Embryonic Stem ◽  
Sequence Motif ◽  
Erythroid Cells ◽  
Gata Factor

GATA-1 is a zinc-finger transcription factor believed to play an important role in gene regulation during the development of erythroid cells, megakaryocytes and mast cells. Other members of the GATA family, which can bind to the same DNA sequence motif, are co-expressed in several of these hemopoietic lineages, raising the possibility of overlap in function. To examine the specific roles of GATA-1 in hematopoietic cell differentiation, we have tested the ability of embryonic stem cells, carrying a targeted mutation in the X-linked GATA-1 gene, to contribute to various blood cell types when used to produce chimeric embryos or mice. Previously, we reported that GATA-1- mutant cells failed to contribute to the mature red blood cell population, indicating a requirement for this factor at some point in the erythroid lineage (L. Pevny et al., (1991) Nature 349, 257–260). In this study, we have used in vitro colony assays to identify the stage at which mutant erythroid cells are affected, and to examine the requirement for GATA-1 in other lineages. We found that the development of erythroid progenitors in embryonic yolk sacs was unaffected by the mutation, but that the cells failed to mature beyond the proerythroblast stage, an early point in terminal differentiation. GATA-1- colonies contained phenotypically normal macrophages, neutrophils and megakaryocytes, indicating that GATA-1 is not required for the in vitro differentiation of cells in these lineages. GATA-1- megakaryocytes were abnormally abundant in chimeric fetal livers, suggesting an alteration in the kinetics of their formation or turnover. The lack of a block in terminal megakaryocyte differentiation was shown by the in vivo production of platelets expressing the ES cell-derived GPI-1C isozyme. The role of GATA-1 in mast cell differentiation was examined by the isolation of clonal mast cell cultures from chimeric fetal livers. Mutant and wild-type mast cells displayed similar growth and histochemical staining properties after culture under conditions that promote the differentiation of cells resembling mucosal or serosal mast cells. Thus, the mast and megakaryocyte lineages, in which GATA-1 and GATA-2 are co-expressed, can complete their maturation in the absence of GATA-1, while erythroid cells, in which GATA-1 is the predominant GATA factor, are blocked at a relatively early stage of maturation.

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.

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