Comparative analysis of the role of mast cells in murine asthma models using Kit‐sufficient mast cell‐deficient animals

Allergy ◽  
2021 ◽  
Author(s):  
Lea Pohlmeier ◽  
Sanchaita Sriwal Sonar ◽  
Hans‐Reimer Rodewald ◽  
Manfred Kopf ◽  
Luigi Tortola
Keyword(s):  
Mast Cell ◽  
Comparative Analysis ◽  
Mast Cells

Mast cell heterogeneity

1984 ◽  
Vol 62 (6) ◽  
pp. 734-737 ◽  
Author(s):  
F. Shanahan ◽  
J. A. Denburg ◽  
J. Bienenstock ◽  
A. D. Befus
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Regulatory Peptides ◽  
Cell Heterogeneity ◽  
Cell Secretion ◽  
Biochemical Basis ◽  
Mucosal Mast Cells ◽  
Mast Cell Heterogeneity

Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell sub-populations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.

Mass cells contribute to O3-induced epithelial damage and proliferation in nasal and bronchial airways of mice

1996 ◽  
Vol 80 (4) ◽  
pp. 1322-1330 ◽  
Author(s):  
M. Longphre ◽  
L. Y. Zhang ◽  
J. R. Harkema ◽  
S. R. Kleeberger
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Dna Synthesis ◽  
Measured Parameter ◽  
Epithelial Injury ◽  
Epithelial Damage ◽  
Proinflammatory Mediators ◽  
Cell Counts ◽  
Air Control

Ozone (O3) exposure produces inflammation in the airways of humans and animal models. However, the mechanism by which O3 affects these changes is uncertain. Mast cells are strategically located below the epithelium of the airways and are capable of releasing a number of proinflammatory mediators. We tested the hypothesis that mast cells contribute to inflammation, epithelial sloughing, and epithelial proliferation in the nasal and terminal bronchiolar murine airways after O3 exposure. Mast cell-sufficient (+/+), mast cell-deficient (W/Wv), and mast cell-repleted [bone marrow-transplanted (BMT) W/Wv] mice were exposed to 2 ppm O3 or filtered air for 3 h. Nasal and bronchoalveolar lavage fluids were collected 6 and 24 h after exposure. Differential cell counts and protein content of the lavage fluids were used as indicators of inflammation and permeability changes in the airways. O3-induced epithelial injury was assessed by light microscopy, and O3-induced DNA synthesis in airway epithelium was estimated by using a 5-bromo-2′-deoxyuridine-labeling index in the nasal and terminal bronchiolar epithelia. Relative to air control mice, O3 caused significant increases in inflammation, epithelial injury, and epithelial DNA synthesis in +/+ mice. There was no significant effect of O3 exposure on any measured parameter in the W/Wv mice. To further assess the role of mast cells in O3-induced epithelial damage, mast cells were restored in W/Wv mice by BMT from +/+ congeners. Relative to sham-transplanted W/Wv mice, O3 caused significant increases in epithelial damage and DNA synthesis as well as inflammatory indicators in BMT W/Wv mice. These observations are consistent with the hypothesis that mast cells significantly modulate the inflammatory and proliferative responses of the murine airways to O3.

The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E2

2018 ◽  
Vol 11 (556) ◽  
pp. eaao4354 ◽  
Author(s):  
Ivana Halova ◽  
Monika Bambouskova ◽  
Lubica Draberova ◽  
Viktor Bugajev ◽  
Petr Draber
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
And Function ◽  
Cell Chemotaxis

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non–T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E2 (PGE2). Although PGE2 does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE2. Stimulation of mast cells that lacked NTAL with PGE2 enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of β1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE2. Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE2, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.

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.

Role of endothelin-converting enzyme, chymase and neutral endopeptidase in the processing of big ET-1, ET-1(1-21) and ET-1(1-31) in the trachea of allergic mice

2002 ◽  
Vol 103 (s2002) ◽  
pp. 353S-356S ◽  
Author(s):  
Benjamin A. DE CAMPO ◽  
Roy G. GOLDIE ◽  
Arco Y. JENG ◽  
Peter J. HENRY
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Response Curve ◽  
Histological Analysis ◽  
Neutral Endopeptidase ◽  
Converting Enzyme ◽  
Rightward Shift ◽  
Endothelin Converting Enzyme ◽  
Mast Cell Chymase

The present study examined the roles of endothelin-converting enzyme (ECE), neutral endopeptidase (NEP) and mast cell chymase as processors of the endothelin (ET) analogues ET-1(1–21), ET-1(1–31) and big ET-1 in the trachea of allergic mice. Male CBA/CaH mice were sensitized with ovalbumin (10µg) delivered intraperitoneal on days 1 and 14, and exposed to aerosolized ovalbumin on days 14, 25, 26 and 27 (OVA mice). Mice were killed and the trachea excised for histological analysis and contraction studies on day 28. Tracheae from OVA mice had 40% more mast cells than vehicle-sensitized mice (sham mice). Ovalbumin (10µg/ml) induced transient contractions (15±3% of the Cmax) in tracheae from OVA mice. The ECE inhibitor CGS35066 (10µM) inhibited contractions induced by big ET-1 (4.8-fold rightward shift of dose-response curve; P<0.05), but not those induced by either ET-1(1–21) or ET-1(1–31). The chymase inhibitors chymostatin (10µM) and Bowman-Birk inhibitor (10µM) had no effect on contractions induced by any of the ET analogues used. The NEP inhibitor CGS24592 (10µM) inhibited contractions induced by ET-1(1–31) (6.2-fold rightward shift; P<0.05) but not ET-1(1–21) or big ET-1. These data suggest that big ET-1 is processed predominantly by a CGS35066-sensitive ECE within allergic airways rather than by mast cell-derived proteases such as chymase. If endogenous ET-1(1–31) is formed within allergic airways, it is likely to undergo further conversion by NEP to more active products.

Arteriolar constriction in skeletal muscle during vascular stunning: role of mast cells

1997 ◽  
Vol 272 (5) ◽  
pp. H2154-H2163 ◽  
Author(s):  
M. W. Keller
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Vascular Reactivity ◽  
Striated Muscle ◽  
Mast Cell Degranulation ◽  
Response Curves ◽  
Maximal Diameter ◽  
Muscle Tissues ◽  
Stimulation Of

Striated muscle becomes stunned during reperfusion after sublethal ischemia. Resistance vessel tone and reactivity are altered in stunned muscle tissues. The hypothesis that adenosine-regulated mast cell degranulation occurs during reperfusion and leads to constriction of resistance arterioles was tested. The hamster cremaster muscle was subjected to 1 h of ischemia followed by reperfusion. Resistance arterioles constricted during reperfusion (74% of maximal diameter at baseline vs. 42% of maximal diameter after 30 min of reperfusion; P < 0.01). Mast cells degranulated in reperfusion concomitant with arteriolar constriction. Stimulation of mast cell degranulation in control animals with compound 48/80 or cold superfusate (21 degrees C) caused vasoconstriction that mimicked that seen in reperfusion. The mast cell stabilizer cromolyn blocked degranulation and constriction. If mast cell granules were depleted by applying compound 48/80 before inducing ischemia, then arterioles failed to constrict during reperfusion. Adenosine A3-antagonist BW-A1433 abolished constriction. These findings suggest that arterioles constrict in reperfusion due to adenosine-regulated mast cell degranulation. Vasodilation in response to sodium nitroprusside and acetylcholine was normal in stunned, constricted arterioles. However, the dose-response curves to adenosine were shifted to the left in arterioles constricted by either stunning, compound 48/80, exposure to cold superfusate, or cromolyn compared with control vessels. Depletion of granular components via stunning, compound 48/80, cold superfusate, or inhibition of secretion with cromolyn results in unopposed A1- or A2-mediated vasodilation in response to adenosine, whereas the dilatory effects of adenosine are blunted by simultaneous release of vasoconstrictors from mast cells in control animals. In summary, it was found that mast cell degranulation occurs during reperfusion and leads to constriction of resistance arterioles and altered vascular reactivity to adenosine. Adenosine is released in ischemia and stimulates mast cell degranulation via the A3 receptor located on mast cells during reperfusion.

scholarly journals The emerging role of mast cell proteases in asthma

2019 ◽  
Vol 54 (4) ◽  
pp. 1900685 ◽  
Author(s):  
Gunnar Pejler
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Current Knowledge ◽  
Secretory Granules ◽  
Cross Linking ◽  
Lysosomal Hydrolases ◽  
Ige Receptor ◽  
Deficient Mice ◽  
Lines Of Evidence

It is now well established that mast cells (MCs) play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on MC-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which MCs influence asthma pathology. MCs contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of MC-restricted proteases. When MCs are activated, e.g. in response to IgE receptor cross-linking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The MC-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly, however, the role of the MC-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, the current knowledge of how the MC-restricted proteases impact on asthma is reviewed.

Pathophysiological Role of Skin Mast Cells in Wound Healing after Scald Injury: Study with Mast Cell-Deficient W/WV Mice

2010 ◽  
Vol 151 (1) ◽  
pp. 80-88 ◽  
Author(s):  
Naotaka Shiota ◽  
Yoriko Nishikori ◽  
Eiichi Kakizoe ◽  
Keiko Shimoura ◽  
Tomomi Niibayashi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mast Cell ◽  
Mast Cells ◽  
Pathophysiological Role ◽  
Scald Injury

scholarly journals Role of Mast Cell-Derived Adenosine in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 2603 ◽  
Author(s):  
Yaara Gorzalczany ◽  
Ronit Sagi-Eisenberg
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Inflammatory Mediators ◽  
Adenosine Receptor ◽  
Tumor Development ◽  
A3 Adenosine Receptor

Accumulating evidence has highlighted the accumulation of mast cells (MCs) in tumors. However, their impact on tumor development remained controversial. Indeed, cumulative data indicate an enigmatic role for MCs in cancer, whereby depending on the circumstances, which still need to be resolved, MCs function to promote or restrict tumor growth. By responding to multiple stimuli MCs release multiple inflammatory mediators, that contribute to the resolution of infection and resistance to envenomation, but also have the potency to promote or inhibit malignancy. Thus, MCs seem to possess the power to define tumor projections. Given this remarkable plasticity of MC responsiveness, there is an urgent need of understanding how MCs are activated in the tumor microenvironment (TME). We have recently reported on the direct activation of MCs upon contact with cancer cells by a mechanism involving an autocrine formation of adenosine and signaling by the A3 adenosine receptor. Here we summarized the evidence on the role of adenosine signaling in cancer, in MC mediated inflammation and in the MC-cancer crosstalk.

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