Increase of Mast Cell-Nerve Association and Neuropeptide Receptor Expression on Mast Cells in Perennial Allergic Rhinitis

2016 ◽  
Vol 23 (5-6) ◽  
pp. 261-270 ◽  
Author(s):  
Duc Dung Le ◽  
David Schmit ◽  
Sebastian Heck ◽  
Albert Joachim Omlor ◽  
Martina Sester ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Mast Cell ◽  
Mast Cells ◽  
Receptor Expression ◽  
Perennial Allergic Rhinitis

The Inferior Turbinate Mast Cell Population of Patients with Perennial Allergic and Nonallergic Rhinitis

1997 ◽  
Vol 11 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Gilead Berger ◽  
Arnon Goldberg ◽  
Dov Ophir
Keyword(s):  
Allergic Rhinitis ◽  
Mast Cell ◽  
Mast Cells ◽  
Inferior Turbinate ◽  
Blue Staining ◽  
Perennial Allergic Rhinitis ◽  
Nonallergic Rhinitis ◽  
Cell Counts ◽  
Significant Difference ◽  
Normal Controls

The number of mast cells in the inferior turbinates of patients with perennial allergic rhinitis and perennial nonallergic rhinitis was compared with normal controls. Mast cell counts expressed as the mean number in 100 high-power fields, assessed after Carnoy's fixation and toluidine blue staining were 1.84 in normal controls (n = 11), 4.39 in patients with perennial allergic rhinitis (n = 13), and 4.00 in those with perennial nonallergic rhinitis (n = 26). Statistical analysis confirmed that the density of mast cells in allergic as well as in nonallergic patients was significantly higher than in normal controls, whereas no significant difference was found between the number of mast cells in allergic and nonallergic patients. It is concluded that the number of mast cells in the inferior turbinate mucosa of patients with perennial rhinitis is increased compared with normal controls, and the increased number is not necessarily allergy-dependent.

Mast cell ultrastructure in the inferior turbinate and stroma of nasal polyps

1997 ◽  
Vol 111 (4) ◽  
pp. 340-345 ◽  
Author(s):  
Adrian Drake-Lee ◽  
Jacqueline Price
Keyword(s):  
Allergic Rhinitis ◽  
Mast Cell ◽  
Mast Cells ◽  
Nasal Polyps ◽  
Inferior Turbinate ◽  
Cell Ultrastructure ◽  
Mast Cell Degranulation ◽  
Perennial Allergic Rhinitis ◽  
Ultrastructural Examination ◽  
Essentially Normal

AbstractFourteen unselected adult patients with nasal polyps had ultrastructural examination of mast cells from matching biopsies of the polyp and inferior turbinate. Between three and 10 blocks were examined for each patient in both tissues and every mast cell that had a nucleus was photographed for study. Fifty-three mast cells were found within the stroma of nasal polyps and 54 in the submucosa of the inferior turbinate biopsies. The number of granules ranged between 13 and 167 (mean 60) for polyps and 18 and 148 (mean 61) in the inferior turbinate. The mast cells appeared essentially normal in the inferior turbinate of four patients. The degree of degranulation of the mast cells was calculated as in previous studies and then averaged for both the polyp and the inferior turbinate of each patient. There was greater degranulation in the nasal polyp compared to inferior turbinate (p= 0.03). These results were compared with mast cell degranulation found in the normal nose and in the inferior turbinate of patients with perennial allergic rhinitis which we previously published. The inferior turbinates in these patients were more degranulated than the normal nose (p= 0.0001) but were similar to that found in patients with perennial allergic rhinitis. This suggested that some degree of degranulation may occur throughout the nose in two thirds of the patients with nasal polyps which supports the theory that mast cell reactions are not limited to the polyps in a proportion of patients.

Mast cell numbers in the mucosa of the inferior turbinate in patients with perennial allergic rhinitis: a light microscopic study

1991 ◽  
Vol 105 (9) ◽  
pp. 736-738 ◽  
Author(s):  
A. B. Drake-Lee ◽  
B. Moriarty ◽  
Lesley A. Smallman
Keyword(s):  
Allergic Rhinitis ◽  
Mast Cell ◽  
Mast Cells ◽  
House Dust ◽  
House Dust Mite ◽  
Inferior Turbinate ◽  
Perennial Allergic Rhinitis ◽  
Cell Numbers ◽  
Dust Mite ◽  
Normal Controls

AbstractThe number of mast cells in the inferior turbinate from patients with perennial allergy due to house dust mite were compared with ten normal controls. Ten random high powered fields were counted in the epithelium and the submucosa in samples which had been divided into two and fixed either in aqueous formaim or Carnoy's fixative. The sections from each block were stained with either Azure A or Chloroacetate esterase technique. No statistical differences were found. The lack of increase in mast cell numbers was attributed to degranulation since numbers have been shown to be increased in perennial allergy when sections are examined ultrastructurally.

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 Beyond IgE: Alternative Mast Cell Activation Across Different Disease States

2020 ◽  
Vol 21 (4) ◽  
pp. 1498 ◽  
Author(s):  
David O. Lyons ◽  
Nicholas A. Pullen
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Autoimmune Disorders ◽  
Receptor Expression ◽  
Mast Cell Activation ◽  
Food Allergies ◽  
Type I ◽  
Disease States ◽  
Ige Mediated

Mast cells are often regarded through the lens of IgE-dependent reactions as a cell specialized only for anti-parasitic and type I hypersensitive responses. However, recently many researchers have begun to appreciate the expansive repertoire of stimuli that mast cells can respond to. After the characterization of the interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis of mast cell activation—a pathway that is independent of the adaptive immune system—researchers are revisiting other stimuli to induce mast cell activation and/or subsequent degranulation independent of IgE. This discovery also underscores that mast cells act as important mediators in maintaining body wide homeostasis, especially through barrier defense, and can thus be the source of disease as well. Particularly in the gut, inflammatory bowel diseases (Crohn’s disease, ulcerative colitis, etc.) are characterized with enhanced mast cell activity in the context of autoimmune disease. Mast cells show phenotypic differences based on tissue residency, which could manifest as different receptor expression profiles, allowing for unique mast cell responses (both IgE and non-IgE mediated) across varying tissues as well. This variety in receptor expression suggests mast cells respond differently, such as in the gut where immunosuppressive IL-10 stimulates the development of food allergy or in the lungs where transforming growth factor-β1 (TGF-β1) can enhance mast cell IL-6 production. Such differences in receptor expression illustrate the truly diverse effector capabilities of mast cells, and careful consideration must be given toward the phenotype of mast cells observed in vitro. Given mast cells’ ubiquitous tissue presence and their capability to respond to a broad spectrum of non-IgE stimuli, it is expected that mast cells may also contribute to the progression of autoimmune disorders and other disease states such as metastatic cancer through promoting chronic inflammation in the local tissue microenvironment and ultimately polarizing toward a unique Th17 immune response. Furthermore, these interconnected, atypical activation pathways may crosstalk with IgE-mediated signaling differently across disorders such as parasitism, food allergies, and autoimmune disorders of the gut. In this review, we summarize recent research into familiar and novel pathways of mast cells activation and draw connections to clinical human disease.

Ultrastructure of nasal mast cells in normal subjects and patients with perennial allergic rhinitis

1991 ◽  
Vol 105 (12) ◽  
pp. 1006-1013 ◽  
Author(s):  
A. B. Drake-Lee ◽  
Jaqueline Price
Keyword(s):  
Allergic Rhinitis ◽  
Mast Cells ◽  
Normal Subjects ◽  
Review Of The Literature ◽  
Perennial Allergic Rhinitis ◽  
House Dust Mite Allergy ◽  
Mite Allergy ◽  
Dust Mite

AbstractThe ultrastructure of mast cells from the nine normal inferior turbinates were compared with those found in eight patients with perennial allergic rhinitis due to house dust mite allergy. Forty-six mast cells from normal patients were found in forty blocks and eighty cells were found in thirty-three blocks in patients with perennial allergy suggesting an increase of mast cell numbers in perennial allergy. There were no basophils outside the blood vessels and whole mast cells were found only in the submucosa. There was no difference in the morphology of cells of different sizes. Mast cells were more degranulated in the allergic mucosa. Degranulation, irrespective of cell size was found at all depths of the mucosa. A review of the literature covered the in vivo and in vitro descriptions of the ultrastructural morphology of human mast cells in the respiratory tract.

Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves

2005 ◽  
Vol 288 (2) ◽  
pp. R491-R500 ◽  
Author(s):  
Michael R. D'Andrea ◽  
Marcia R. Saban ◽  
Norma P. Gerard ◽  
Barry K. Wershil ◽  
Ricardo Saban
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Spatial Association ◽  
Spatial Relationship ◽  
Genetically Engineered ◽  
Receptor Expression ◽  
Wild Type ◽  
Genetically Engineered Mice ◽  
Neurokinin 1 ◽  
Anatomic Relationship

A spatial association between mast cells and nerves has been described in both the gastrointestinal and genitourinary tracts. However, the factors that influence the anatomic relationship between mast cells and nerves have not been completely defined. It has been suggested that the high-affinity receptor for substance P [neurokinin-1 (NK1)] might modulate this interaction. We therefore assessed mast cell-nerve relationships in tissues isolated from wild-type and NK1 receptor knockout (NK1−/−) mice. We now report that, in the complete absence of NK1 receptor expression, there is a significant increase in the number of mast cells without a change in the anatomic relationship between mast cell and nerves in stomach and bladder tissues at the light microscopic level. We next determined whether transplanted mast cells would maintain their spatial distribution, number, and contact with nerve elements. For this purpose, mast cell-deficient Kit W /Kit W−v mice were reconstituted with wild-type or NK1−/− bone marrow. No differences in mast cell-nerve contact were observed. These results suggest that NK1 receptor expression is important in the regulation of the number of mast cells but is not important in the interaction between mast cells and nerves. Furthermore, the interaction between mast cells and nerves is not mediated through NK1 receptor expression on the mast cell. Further studies are needed to determine the molecular pathway involved in mast cell migration and interaction with nerve elements, but the model of reconstitution of Kit W /Kit W−v mice with mast cells derived from different genetically engineered mice is a useful approach to further explore these mechanisms.

scholarly journals AK002, a Novel Humanized Monoclonal Antibody to Siglec-8, Inhibits Mast Cell Activity and Depletes Eosinophils in Ex Vivo Bone Marrow Tissue from Patients with Systemic Mastocytosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1104-1104 ◽  
Author(s):  
Bradford A Youngblood ◽  
Emily C Brock ◽  
John Leung ◽  
Alan T Chang ◽  
Christopher Bebbington ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Mast Cell ◽  
Mast Cells ◽  
Ex Vivo ◽  
Systemic Mastocytosis ◽  
Cell Activity ◽  
Receptor Expression ◽  
Long Term Treatment

Abstract INTRODUCTION: Systemic Mastocytosis (SM) is a rare disease characterized by the clonal proliferation and accumulation of mast cells in the bone marrow, respiratory and gastrointestinal tracts, and organs such as the skin, liver, spleen, and brain. Common symptoms include pruritus, flushing, headache, cognitive impairment, fatigue, diarrhea, abdominal pain, hypotension and skin lesions, as well as an increased risk for osteoporosis and anaphylaxis. SM is currently managed with antihistamines, cromolyn sodium, and leukotriene blocking agents, which lack specificity and efficacy. In addition, glucocorticoids can provide temporary relief in some cases; however long-term treatment with steroids is not appropriate due to their many side effects. Siglec-8 is an inhibitory receptor selectively expressed on human mast cells and eosinophils, and therefore represents a novel target for the treatment of SM. Antibodies to Siglec-8 have been shown to inhibit mast cell activity and induce apoptosis of eosinophils. AK002 is a novel, humanized, non-fucosylated IgG1 monoclonal antibody to Siglec-8. This study evaluates the expression of Siglec-8 and ex vivo activity of AK002 on mast cells and eosinophils in bone marrow biopsies from patients with SM. METHODS: Bone marrow aspirates were obtained from patients clinically diagnosed with SM and processed to remove red blood cells. Multi-color flow cytometry was used to quantify eosinophils and mast cells and to evaluate the activation state of mast cells. The ex vivo activity of AK002 against eosinophils and mast cells was evaluated by flow cytometry. The inhibitory activity of AK002 agaist mast cells was also examined by quantifying cytokine levels in cultured bone marrow aspirate supernatants. RESULTS: All mast cells and eosinophils in bone marrow aspirates from SM patients displayed high Siglec-8 receptor expression (Figure 1). These mast cells also expressed the SM specific markers, CD25 (Figure 1) and CD30 and increased levels of cell surface degranulation markers. The expression of CD25 on mast cells significantly decreased following overnight treatment with AK002. AK002 also significantly reduced the level of mast cell-associated cytokines produced in cultured bone marrow supernatants, including IL-6, IL-8, and TNFα (Figure 2A). These changes in mast cell activity after AK002 treatment were not due to a reduction in mast cell numbers. In contrast, overnight incubation of AK002 significantly reduced the number of bone marrow eosinophils compared to an isotype control (Figure 2B). CONCLUSIONS: Bone marrow aspirates from patients with SM had activated mast cells and eosinophils that displayed robust expression of Siglec-8. AK002 demonstrated SM mast cell inhibition in ex vivo bone marrow aspirates. AK002 also had depleting effects on eosinophils, which may be valuable to SM patients with associated eosinophilia. These encouraging results could represent a novel approach for the treatment of SM. Disclosures Youngblood: Allakos, Inc.: Employment. Brock:Allakos, Inc.: Employment. Leung:Allakos, Inc.: Employment. Chang:Allakos, Inc.: Employment. Bebbington:Allakos, Inc.: Employment. Tomasevic:Allakos, Inc.: Employment.

scholarly journals Effect of NK1 receptor expression on mast cells on nerve-mast cell communication

2003 ◽  
Vol 43 (supplement) ◽  
pp. S164
Author(s):  
T. Furuno ◽  
John Bienenstock ◽  
M. Nakanishi
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Communication ◽  
Receptor Expression ◽  
Nk1 Receptor
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