Tag: mast

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Does ?-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of ?-Hexosaminidase in Mast Cell Granules.

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Does ?-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of ?-Hexosaminidase in Mast Cell Granules.

J Immunol. 2014 Jul 11;

Authors: Fukuishi N, Murakami S, Ohno A, Yamanaka N, Matsui N, Fukutsuji K, Yamada S, Itoh K, Akagi M

Abstract
?-Hexosaminidase, which is generally present in the lysosome, is essential for glycoprotein metabolism in the maintenance of cell homeostasis. In mast cells (MCs), large amounts of ?-hexosaminidase are present in the granules as opposed to the lysosome, and the biological role of MC ?-hexosaminidase has yet to be fully elucidated. Therefore, we investigated the biological role of ?-hexosaminidase in MC granules. Bone marrow-derived MCs from C57BL/6 (BL/6-BMMC) or ?-hexosaminidase gene-deficient (hexb(-/-)-BMMC) mice were transplanted into MC-deficient (WBB6F1/J-Kit(W)/Kit(W-v) [W/W(v)]) mice to generate MC-reconstituted models. In asthma model experiments, no differences were observed in the symptoms of BL/6, W/W(v), BL/6-BMMC-reconstituted W/W(v), or hexb(-/-)-BMMC-reconstituted W/W(v) mice. In Staphylococcus epidermidis experimental infection model experiments, the severity of symptoms and frequency of death were markedly higher in W/W(v) and hexb(-/-)-BMMC-reconstituted W/W(v) mice than in BL/6 and BL/6-BMMC-reconstituted W/W(v) mice. The growth of S. epidermidis in an in vitro study was clearly inhibited by addition of BL/6-BMMC lysate, but not by addition of hexb(-/-)-BMMC lysate. Moreover, suppression of bacterial proliferation was completely recovered when bacteria were incubated with hexb(-/-)-BMMC lysate plus ?-hexosaminidase. Transmission electron microscopy indicated that the cell wall of S. epidermidis was heavily degraded following coincubation of bacteria with BL/6-BMMC lysate, but not following coincubation with hexb(-/-)-BMMC lysate. These findings strongly suggest that MC granule ?-hexosaminidase is crucial for defense against bacterial invasion, but is not involved in the allergic response. Our results also suggest that the bactericidal mechanism of ?-hexosaminidase involves degradation of bacterial cell wall peptidoglycan.

PMID: 25015817 [PubMed – as supplied by publisher]

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SHP-1 Regulation of Mast Cell Function in Allergic Inflammation and Anaphylaxis.

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SHP-1 Regulation of Mast Cell Function in Allergic Inflammation and Anaphylaxis.

PLoS One. 2013;8(2):e55763

Authors: Zhou L, Oh SY, Zhou Y, Yuan B, Wu F, Oh MH, Wang Y, Takemoto C, Van Rooijen N, Zheng T, Zhu Z

Abstract
Allergic inflammation and severe allergic reactions (anaphylaxis) are important in allergen induced diseases. Bacterial products such as lipopolysaccharide (LPS) are ubiquitous and can facilitate allergen induced Th2 immune responses. Phosphatase SHP-1 is critical in regulating immunological homeostasis and in allergen induced Th2 immune responses in the lung. However, the mechanisms underlying the initiation of allergic inflammation and allergen induced anaphylaxis are still not completely elucidated and it is unclear whether SHP-1 plays any role in LPS-induced airway inflammation and in allergen-induced anaphylaxis. In this study we tested the hypothesis that phosphatase SHP-1 plays an important role in allergic inflammation and anaphylaxis and determined whether its effects are through regulation of mast cell functions. SHP-1 deficient (mev/+ and mev/mev) and mast cell deficient (Kit(W-sh)) mice were examined in their responses to LPS airway stimulation and to ovalbumin (OVA) allergen induced systemic anaphylaxis. Compared to wild type mice, mev/+ mice had significantly enhanced LPS induced airway inflammation and OVA induced anaphylactic responses, including hypothermia and clinical symptoms. These changes were mast cell dependent as Kit(W-sh) mice had reduced responses whereas adoptive transfer of mast cells restored the responses. However, T and B cells were not involved and macrophages did not play a significant role in LPS induced airway inflammation. Interestingly, basophil differentiation from SHP-1 deficient bone marrow cells was significantly reduced. These findings provided evidence that through regulation of mast cell functions SHP-1 plays a critical role as a negative regulator in allergic inflammation and in allergen induced anaphylaxis. In addition, SHP-1 seems to be required for normal basophil development.

PMID: 23390550 [PubMed – in process]

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Role of female sex hormones, estradiol and progesterone, in mast cell behavior.

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Role of female sex hormones, estradiol and progesterone, in mast cell behavior.

Front Immunol. 2012;3:169

Authors: Zierau O, Zenclussen AC, Jensen F

Abstract
Female sex hormones have long been suspected to have an effect on mast cell (MC) behavior. This assumption is based on the expression of hormone receptors in MCs as well as on the fact that many MC-related pathophysiological alterations have a different prevalence in females than in males. Further, serum IgE levels are much higher in allergic female mice compared to male mice. Ovariectomized rats developed less airway inflammation compared to sham controls. Following estrogen replacement ovariectomized rats re-established airway inflammation levels’ found in intact females. In humans, a much higher asthma prevalence was found in women at reproductive age as compared to men. Serum levels of estradiol and progesterone have been directly correlated with the clinical and functional features of asthma. Around 30-40% of women who have asthma experienced worsening of their symptoms during the perimenstrual phase, the so-called perimenstrual asthma. Postmenopausal women receiving hormone replacement therapy have an increased risk of new onset of asthma. Beside, estrus cycle dependent changes on female sex hormones are related to changes on MC number in mouse uterine tissue and estradiol and progesterone were shown to induce uterine MC maturation and degranulation. We will discuss here the currently available information concerning the role of these female sex hormones on MC behavior.

PMID: 22723800 [PubMed – in process]

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Amaranthus spinosus Linn. inhibits mast cell-mediated anaphylactic reactions.

Amaranthus spinosus Linn. inhibits mast cell-mediated anaphylactic reactions.

J Immunotoxicol. 2011 Dec 6;

Authors: Patil SD, Patel MR, Patel SR, Surana SJ

Abstract
The current study characterizes the mechanism by which the Amaranthus spinosus (Amaranthaceae) decreases mast cell-mediated anaphylactic reactions. Anaphylaxis is a typical hypersensitivity Type I reaction, sharing common mechanisms with asthma in its early and late phases. Mast cells are key as effector cells in hypersensitivity Type I reactions. A. spinosus has been traditionally used in the treatment of allergic bronchitis and asthma, but its role in mast cell-mediated anaphylactic reactions has not fully been investigated. This report investigated the potential effects of the ethyl acetate fraction of A. spinosus leaves (EAFAS) against a Compound 48/80 (potent secretagogue)-induced systemic anaphylactic shock paradigm in a mouse model. In addition, rat peritoneal mast cells (RPMC) were used in in vitro studies to investigate the effect of EAFAS on Compound 48/80-induced peritoneal mast cell degranulation and histamine release. When administration by the oral route-1?h before Compound 48/80 injection-EAFAS (at dose from 0.001-1?g/kg) completely inhibited the induced anaphylactic shock. EAFAS at concentrations ranging 0.25-1?mg/ml dose-dependently attenuated rates of mast cell degranulation and histamine release from RPMC that were evoked by Compound 48/80. The results of the present investigation indicated that EAFAS stabilizes the mast cell lipid bilayer membrane, thereby preventing the perturbation of membrane and the release of histamine. As a result of these anti-degranulating and anti-histaminic effects, it can be suggested that EAFAS may have a potential use in the prophylaxis and management of anaphylactic reactions.

PMID: 22145857 [PubMed – as supplied by publisher]

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