Cell Archives - Page 2 of 3 - World Asthma Foundation

July 15, 2014

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

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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February 4, 2014

Respiratory syncytial virus and seasonal influenza cause similar illnesses in children with sickle cell disease.

Respiratory syncytial virus and seasonal influenza cause similar illnesses in children with sickle cell disease.

Pediatr Blood Cancer. 2014 Jan 31;

Authors: Sadreameli SC, Reller ME, Bundy DG, Casella JF, Strouse JJ

Abstract
BACKGROUND: Respiratory syncytial virus (RSV) is a cause of acute chest syndrome (ACS) in sickle cell disease (SCD), but its clinical course and acute complications have not been well characterized. We compared RSV to seasonal influenza infections in children with SCD.
PROCEDURE: We defined cases as laboratory-confirmed RSV or seasonal influenza infection in inpatients and outpatients <18 years of age with SCD from 1 September 1993 to 30 June 2011. We used Fisher’s exact test to compare proportions, Student’s t-test or Wilcoxon rank-sum test to compare continuous variables, and logistic regression to evaluate associations.
RESULTS: We identified 64 children with RSV and 91 with seasonal influenza. Clinical symptoms, including fever, cough, and rhinorrhea were similar for RSV and influenza, as were complications, including ACS and treatments for SCD. In a multivariable logistic regression model, older age (OR 1.2 per year, 95% CI [1.02-1.5], P?=?0.04), increased white blood cell count at presentation (OR 1.1 per 1,000/?l increase, 95% CI [1.03-1.3], P?=?0.008), and a history of asthma (OR 7, 95% [CI 1.3-37], P?=?0.03) were independently associated with increased risk of ACS in children with RSV. The hospitalization rate for children with SCD and RSV (40 per 1,000 <5 years and 63 per 1,000 <2 years) greatly exceeds the general population (3 in 1,000 <5 years).
CONCLUSIONS: We conclude that RSV infection is often associated with ACS and similar in severity to influenza infection in febrile children with SCD. Pediatr Blood Cancer 2014;9999:1-4. © 2014 Wiley Periodicals, Inc.

PMID: 24481883 [PubMed – as supplied by publisher]

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May 9, 2013

The rabbit as a model for studying lung disease and stem cell therapy.

The rabbit as a model for studying lung disease and stem cell therapy.

Biomed Res Int. 2013;2013:691830

Authors: Kamaruzaman NA, Kardia E, Kamaldin N’, Latahir AZ, Yahaya BH

Abstract
No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

PMID: 23653896 [PubMed – in process]

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February 8, 2013

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

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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February 7, 2013

Inflammation signals airway smooth muscle cell proliferation in asthma … – 7thSpace Interactive (press release)

Inflammation signals airway smooth muscle cell proliferation in asthma …
7thSpace Interactive (press release)
It is now well recognized that chronic inflammation, as well as airway hyper-responsiveness and remodeling of airway during inflammation, are crucial to asthma. ASM is caused by increased cell proliferation or by hypertrophy of ASM cells depending on …

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November 25, 2012

Programmed cell death ligand 2 regulates T(H)9 differentiation and induction of chronic airway hyperreactivity.

Programmed cell death ligand 2 regulates T(H)9 differentiation and induction of chronic airway hyperreactivity.

J Allergy Clin Immunol. 2012 Nov 19;

Authors: Kerzerho J, Maazi H, Speak AO, Szely N, Lombardi V, Khoo B, Geryak S, Lam J, Soroosh P, Van Snick J, Akbari O

Abstract
BACKGROUND: Asthma is defined as a chronic inflammatory disease of the airways; however, the underlying physiologic and immunologic processes are not fully understood. OBJECTIVE: The aim of this study was to determine whether T(H)9 cells develop in vivo in a model of chronic airway hyperreactivity (AHR) and what factors control this development. METHOD: We have developed a novel chronic allergen exposure model using the clinically relevant antigen Aspergillus fumigatus to determine the time kinetics of T(H)9 development in vivo. RESULTS: T(H)9 cells were detectable in the lungs after chronic allergen exposure. The number of T(H)9 cells directly correlated with the severity of AHR, and anti-IL-9 treatment decreased airway inflammation. Moreover, we have identified programmed cell death ligand (PD-L) 2 as a negative regulator of T(H)9 cell differentiation. Lack of PD-L2 was associated with significantly increased TGF-? and IL-1? levels in the lungs, enhanced pulmonary T(H)9 differentiation, and higher morbidity in the sensitized mice. CONCLUSION: Our findings suggest that PD-L2 plays a pivotal role in the regulation of T(H)9 cell development in chronic AHR, providing novel strategies for modulating adaptive immunity during chronic allergic responses.

PMID: 23174661 [PubMed – as supplied by publisher]

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June 25, 2012

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

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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May 10, 2012

New Cell Type with a Key Role in Treatment-Resistant Asthma Discovered – news Stories

Science Codex

New Cell Type with a Key Role in Treatment-Resistant Asthma Discovered
news Stories
Researchers from the University of Michigan (UM) Health System have discovered a new type of cell in mice that appears to be crucial to causing asthma symptoms—even in the presence of steroid. Their findings, published in the journal Nature Medicine, …
Cell as target for tough-to-treat asthmaFuturity: Research News

all 3 news articles »

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May 8, 2012

Cell as target for tough-to-treat asthma – Futurity: Research News

CBS Local

Cell as target for tough-to-treat asthma
Futurity: Research News
For most people with asthma, a couple of puffs from an inhaler filled with steroids makes breathing easy. But if their lungs become resistant to the calming effect of that medicine, they live in fear of severe asthma attacks that could send them to the …
University of Michigan researchers identify cells resistant to asthma treatmentsAnnArbor.com
Scientists discover new type of cell with a key role in treatment-resistant asthmaSacramento Bee

all 22 news articles »

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May 7, 2012

Scientists discover new type of cell with a key role in treatment-resistant asthma – MarketWatch (press release)

Scientists discover new type of cell with a key role in treatment-resistant asthma
MarketWatch (press release)
For most people with asthma, a couple of puffs from an inhaler filled with steroids makes breathing easy. But if their lungs become resistant to the calming effect of that medicine, they live in fear of severe asthma attacks that could send them to the …

and more »

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