Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells

Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin E–mediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cell–related cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin E–mediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells.     

Inhibitory effect of honeybee-collected pollen on mast cell degranulation in vivo and in vitro

Bee-collected pollen (bee pollen [BP]) has been used as a folk medicine for centuries against various diseases, including allergy. There is no study elucidating how BP exerts such an anti-allergic effect. Since mast cells play a central role in the pathogenesis of various allergic diseases, we investigated the effect of BP on mast cell activation elicited by the Fc immunoglobulin E (IgE) receptor (Fc epsilon RI)-mediated pathways. The in vivo effect of orally administered BP on cutaneous mast cell activation was examined by passive cutaneous anaphylaxis reaction. In vitro mast cell degranulation and IgE binding to mast cells and the status of protein tyrosine phosphorylation were examined using bone marrow-derived mast cells. Daily oral administration of BP to mice significantly reduced the cutaneous mast cell activation elicited by IgE and specific antigens. BP also reduced in vitro mast cell degranulation and tumor necrosis factor-alpha production by inhibiting IgE binding to Fc epsilon RI on mast cells. The inhibitory effect of BP on mast cell degranulation by preventing IgE binding was confirmed by the reduced levels of protein tyrosine phosphorylation, which occurred as downstream events in activated mast cells via Fc epsilon RI. These results first revealed that the anti-allergic action of BP was exerted by inhibiting the Fc epsilon RI-mediated activation of mast cells, which plays important roles, not only in the early phase, but also in the late phase of allergic reactions.     

Maternal Bisphenol A Exposure Promotes the Development of Experimental Asthma in Mouse Pups

Background

We recently reported that various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro.

Objectives

We hypothesized that environmental estrogens would enhance allergic sensitization as well as bronchial inflammation and responsiveness. To test this hypothesis, we exposed fetal and neonatal mice to the common environmental estrogen bisphenol A (BPA) via maternal loading and assessed the pups’ response to allergic sensitization and bronchial challenge.

Methods

Female BALB/c mice received 10 μg/mL BPA in their drinking water from 1 week before impregnation to the end of the study. Neonatal mice were given a single 5 μg intraperitoneal dose of ovalbumin (OVA) with aluminum hydroxide on postnatal day 4 and 3% OVA by nebulization for 10 min on days 13, 14, and 15. Forty-eight hours after the last nebulization, we assessed serum IgE antibodies to OVA by enzyme-linked immunosorbent assay (ELISA) and airway inflammation and hyperresponsiveness by enumerating eosinophils in bronchoalveolar lavage fluid, whole-body barometric plethysmography, and a forced oscillation technique.

Results

Neonates from BPA-exposed mothers responded to this “suboptimal” sensitization with higher serum IgE anti-OVA concentrations compared with those from unexposed mothers (p < 0.05), and eosinophilic inflammation in their airways was significantly greater. Airway responsiveness of the OVA-sensitized neonates from BPA-treated mothers was enhanced compared with those from unexposed mothers (p < 0.05).

Conclusions

Perinatal exposure to BPA enhances allergic sensitization and bronchial inflammation and responsiveness in a susceptible animal model of asthma.     

Selenium Modulates the Allergic Response to Whey Protein in a Mouse Model for Cow’s Milk Allergy

Cow’s milk allergy is a common food allergy in infants, and is associated with an increased risk of developing other allergic diseases. Dietary selenium (Se), one of the essential micronutrients for humans and animals, is an important bioelement which can influence both innate and adaptive immune responses. However, the effects of Se on food allergy are still largely unknown. In the current study it was investigated whether dietary Se supplementation can inhibit whey-induced food allergy in an animal research model. Three-week-old female C3H/HeOuJ mice were intragastrically sensitized with whey protein and cholera toxin and randomly assigned to receive a control, low, medium or high Se diet. Acute allergic symptoms, allergen specific immunoglobulin (Ig) E levels and mast cell degranulation were determined upon whey challenge. Body temperature was significantly higher in mice that received the medium Se diet 60 min after the oral challenge with whey compared to the positive control group, which is indicative of impaired anaphylaxis. This was accompanied by reductions in antigen-specific immunoglobulins and reduced levels of mouse mast cell protease-1 (mMCP-1). This study demonstrates that oral Se supplementation may modulate allergic responses to whey by decreasing specific antibody responses and mMCP-1 release.     

Guidelines for the diagnosis, treatment and management of mastocytosis

Mastocytosis consists of a group of disorders characterized by a pathologicincrease in mast cells in tissues including skin, bone marrow, liver, spleen, andlymph nodes. Mastocytosis is a rare disease and general practitioners have limited exposure to its clinical manifestations, diagnosis, classification, and management. Moreover a complete and clear review in this field is not easy founded. Diagnosis of mastocytosis is suspected on clinical grounds and is established by histopathologic examination of involved tissues such as skin and bone marrow. The most common clinical sign of mastocytosis is the presence of typical skin lesions of urticaria pigmentosa. Most patients experience symptoms related to mast cell mediator release, and prevention of the effects of these mediators on tissues constitutes the major therapeutic goal in the management of mastocytosis. Despite recent advances in knowledge about the pathophysiology, diagnosis, and classification of mastocytosis, a curative treatment for mastocytosis does not now exist; furthermore mastocytosis is a chronic diseases with different severity grades but in all of them with an important negative impact on quality of live of patients. Management of patients within all categories of mastocytosis includes: 1. A careful counselling of patients (parents in paediatric cases) and care providers. 2. Avoidance of factors triggering acute mediator release. 3. Treatment of acute mast cell mediator release. 4. Treatment of chronic mast cell mediator release, and if indicated. 5. An attempt to treat organ infiltration by mast cells. The goal of this review is to provide a practical guide focus on diagnostic criteria for the different treatment options currently available and their management.     

Influence of polyphenols on allergic immune reactions: mechanisms of action

The increased incidence of allergic disease seems to rely on many factors. Among them, the association between genetic variations of the immune response and environmental pressure by allergens, infectious agents and pollutants should be taken into consideration. In alternative to conventional treatments with corticosteroids and antihistaminics, nutraceuticals have been shown to act on allergic disease either during allergic sensitisation or on consolidated disease. In this review, special emphasis is placed on the effects of dietary polyphenols on three major allergic diseases, namely atopic eczema, food allergy and asthma. Interference of polyphenols with T-helper 2 activation seems to be the main mechanism of their inhibitory effects on allergy development. Moreover, deficits of T-regulatory cells seem to play a pathogenic role in allergic disease and, therefore, these cells may represent a major target of polyphenol activity.     

Histamine release from mast cells by terpenoid aldehydes isolated from glanded varieties of cotton

In vivo and in vitro experiments have strongly indicated that mast cell degranulation, with its release of histamine and other pharmacoactive compounds, plays a major role in the acute respiratory response of humans following inhalation of cotton textile dust. Thirteen terpenoid aldehydes isolated from the glands of the two major Gossypium species used for cotton production, stimulated significant release of histamine from mast cells at concentrations of 1 micrograms/mL. Eleven of the thirteen compounds produce significant mast cell degranulation at concentrations well below the levels of free terpenoid aldehydes that could be expected to enter the lungs during an eight hour work day under the current permissible card room standards of 200 micrograms per cubic meter. Daily mast cell degranulation, stimulated by these terpenoid aldehydes could account for many of the pathophysiological changes found in the chronic byssinotic.     

164例儿童过敏性疾病血清过敏原检测分析

目的:探讨血清过敏原检测在儿童过敏性疾病中的意义。方法:对164例过敏性疾病儿童的血清过敏原检测结果进行回顾分析。结果:164例患过敏性疾病患儿中147例血清总IgE阳性,阳性率为89.6%。吸入组阳性率70.7%,食物组阳性率18.9%,混合阳性率18.9%。过敏原检测阳性率最高者为荨麻疹,其次支气管哮喘、过敏性鼻炎及湿疹。检出的阳性过敏原中,吸入组最常见为户尘螨(116例,占70.7%),食物组最常见为虾蟹(31例,占18.9%)。结论:吸入性过敏原和食物过敏原均是引起儿童过敏性疾病的重要原因。血清过敏原测定有利于了解患者的过敏状态,协助过敏性疾病的诊断,为过敏性疾病制定环境干预措施和免疫治疗方案提供可靠依据。     

Neuronal plasticity in persistent perennial allergic rhinitis

OBJECTIVE: Persistent perennial allergic rhinitis belongs to the most frequent diseases in occupational and environmental medicine. Because the innervation may play a role in the pathogenesis of the disease, the present study analyzed nasal mucosal nerve profiles. METHODS: Neuropeptide-containing nerve fibers were examined using immunohistochemistry and related to eosinophil and mast cell numbers. RESULTS: In contrast to constant numbers of mast cells, there was a significant increase in the number of eosinophils. Immunohistochemistry for calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and neuropeptide tyrosine (NPY) revealed abundant staining of mucosal nerves. Semiquantitative assessment of nerve fiber neuropeptide density demonstrated a significant increase of VIP-positive fibers in rhinitis tissues. CONCLUSIONS: The present data indicate a differential regulation of neuropeptide-containing nerve fibers with increased numbers of VIPergic fibers suggesting a modulatory role of the upper airway innervation in perennial allergic rhinitis.     

How exposure to environmental tobacco smoke, outdoor air pollutants, and increased pollen burdens influences the incidence of asthma

Asthma is a multifactorial airway disease that arises from a relatively common genetic background interphased with exposures to allergens and airborne irritants. The rapid rise in asthma over the past three decades in Western societies has been attributed to numerous diverse factors, including increased awareness of the disease, altered lifestyle and activity patterns, and ill-defined changes in environmental exposures. It is well accepted that persons with asthma are more sensitive than persons without asthma to air pollutants such as cigarette smoke, traffic emissions, and photochemical smog components. It has also been demonstrated that exposure to a mix of allergens and irritants can at times promote the development phase (induction) of the disease. Experimental evidence suggests that complex organic molecules from diesel exhaust may act as allergic adjuvants through the production of oxidative stress in airway cells. It also seems that climate change is increasing the abundance of aeroallergens such as pollen, which may result in greater incidence or severity of allergic diseases. In this review we illustrate how environmental tobacco smoke, outdoor air pollution, and climate change may act as environmental risk factors for the development of asthma and provide mechanistic explanations for how some of these effects can occur.     

广州市儿童常见过敏性疾病的过敏原检测结果分析

目的了解广州市儿童常见过敏性疾病的过敏原分布状况,为不同过敏性疾病患儿的环境过敏原防治提供依据。方法纳入喘息性疾病及哮喘(1013例)、过敏性鼻炎(660例)、过敏性结膜炎(422例)、湿疹(2762例)、特应性皮炎(831例)和荨麻疹(1181例)患儿共6869例,经免疫印迹法检测血清过敏原E型特异性抗体(sIgE),并对检测结果进行统计学描述和分析。结果在6869例患儿中,过敏原sIgE阳性总检出率为74.01%,男性患儿阳性率(75.02%)高于女性患儿(72.25%),吸入性过敏原阳性率(53.47%)低于食入性过敏原(57.39%)。尘螨和牛奶分别是阳性率最高的吸入性过敏原和食入性过敏原。婴幼儿期患儿最常见的过敏性疾病是湿疹;学龄期患儿常见过敏性鼻炎和荨麻疹。结论广州地区导致儿童过敏性疾病的主要过敏原为尘螨和牛奶。不同类型的过敏性疾病的过敏原不相同,应该根据不同类型过敏性疾病的主要过敏原采取针对性防治措施。     

食物致敏性评价RBL-2H3细胞模型的研究

目的 研究大鼠嗜碱性白血病粒细胞(ra basophil leukemia cells,RBL-2H3细胞)用于食物致敏性评价的可行性。 方法 实验组和对照组动物血清按照不同倍数稀释,包括1:4、1:8、1:16、1:32、1:64、1:128、1:256和1:512,将稀释后的血清分别与RBL-2H3细胞孵育4 h,然后用MEM完全培养基重新培养24 h。最后,向细胞分别加入含有10 μg/ml和100 μg/ml OVA的MEM溶液,孵育45 min,测定上清液中β-氨基己糖苷酶含量和细胞内总的β-氨基己糖苷酶含量,计算β-氨基己糖苷酶释放率。 结果 对比不同的蛋白刺激浓度发现:100 μg/ml OVA刺激后,稀释比例为1:4、1:8、1:16和1:32时,实验组和对照组差异有统计学意义(P<0.05,P<0.01);10 μg/ml OVA刺激后,稀释比例仅1:4、1:8和1:16时,实验组和对照组差异有统计学意义(P<0.05,P<0.01)。对比不同的血清稀释倍数发现,1:4倍稀释时实验组β-氨基己糖苷酶释放率显著高于稀释比例1:256实验组,差异有统计学意义(P<0.05)。 结论 初步建立了RBL-2H3细胞致敏模型,以期用于食物致敏性评价中。     

Multiple chemical sensitivity (MCS) and others: allergological,environmental and psychological investigations in individuals with indoor air related complaints

Clinical observations point to an expanding group of individuals attributing hypersensitivity phenomena to indoor air pollution. It was the aim of this study to characterize such subjects by an interdisciplinary approach. Sixty-five individuals, recruited by a public campaign, were studied by a thorough allergological examination and a structured psychological interview. Measurements of common indoor pollutants in the air and in the dust were performed in rooms of several selected patients. Forty-two patients (65%) revealed a sensitization to common allergens, out of these 32 (49%) to house dust mites. Thirty-eight (58%) patients showed a psychosomatic or psychotic disorder. Increased concentrations of at least one of the measured indoor air pollutants were found in 11 out of 13 investigated houses. According to these results, four groups of patients could be identified: Seventeen patients (26%) had "classic" allergic diseases treated inadequately. In 19 patients (29%) allergic diseases were superimposed by strong psychosomatic interactions. An exclusive psychosomatic or psychotic cause of the complaints was found in 19 (29%). Ten subjects (16%) had "classic" allergic diseases (e.g. allergic rhinoconjunctivitis, urticaria), however, there were additional indications of hypersensitivity reactions to components other than classical allergens. Patients presenting with hypersensitivity phenomena attributed by themselves to indoor air pollution are a heterogeneous group and need a diligent work-up including intense allergological examination. The role of increased concentrations of indoor air pollutants has to be elucidated further.     

An antioxidant agent prevents NO2-induced inhibition of mast cell mediator release: evidence that the mechanism involves free radicals.

Previously we established that in vitro NO2 exposure induced inhibition of histamine release from rat peritoneal mast cells (PMC) stimulated with secretagogues such as compound 48/80 or substance P. To further explore the effects of NO2 exposure on mast cells, we investigated whether the addition of an antioxidant agent, 2-mercaptoethanol (2-ME), can prevent NO2-induced inhibition of mediator release from PMC. Histamine release from 5 ppm NO2-exposed PMC stimulated with 10 and 20 microM substance P was significantly inhibited compared with that from the controls. beta-Hexosaminidase release from 5 ppm NO2-exposed PMC stimulated with 20 microM substance P was also significantly inhibited. However, the inhibition of both histamine and beta-hexosaminidase release from exposed PMC was diminished by the addition of 5 mM 2-ME during NO2 exposure. Although IgE-mediated histamine release from NO2 exposed PMC was markedly inhibited, the addition of 5 mM 2-ME during NO2 exposure induced no inhibition of histamine release. These results suggest a possible relationship between NO2-induced inhibition of mast cell mediator release and production of free radicals by the action of NO2.     

Occupational respiratory allergopathies: environmental monitoring, air allergens, prevention

The prevalence of allergic diseases has increased over recent years. Several epidemiological studies have been undertaken to determine the prevalence and the incidence of asthma and/or rhinitis caused by occupational allergens, and to investigate the factors that may affect their occurrence. In the last decade, with the development of methods to measure airborne allergens concentrations. Studies have been undertaken to examine the relationship between the levels of airborne allergens and the development of symptoms. In this paper we have reviewed the main studies published on the topic, and focused our attention on three aeroallergens (wheat flour proteins, latex and laboratory animal allergens), that have been thoroughly investigated in literature, from both clinical, epidemiological and laboratory aspects, which highlighted the major responsible allergens and tried to set up the dose-response relationship for symptoms and for sensitization. These studies cannot be directly compared to each other because of differences in the methods; however they seem to suggest that low levels of airborne allergens may be sufficient to sensitize individuals. In contrast, the evidence for a dose-response relationship between exposure and symptoms is indirect and not always clear. Further epidemiological studies are necessary. In occupational medicine the presence of asthma or of another allergic disease in a severe form is suggested as a criterion for excluding workers from their job. Workers that do not manifest allergic symptoms but are atopic should be informed about the risk of developing occupational respiratory diseases, and periodic check-ups are strongly recommended. Medical controls must not be disconnected from environmental controls. Standardized methods of measurement of airborne allergens for environmental control need to be set in order to allow comparison between studies and to adopt primary prevention measures.     

Current views on allergic diseases

Allergic diseases are an increasing health problem in the industrialised and developed countries especially in children and young adult persons. They are considered diseases of modern civilisation. The reported cumulative prevalence of allergic diseases in childhood of 25-30% includes allergic rhinoconjunctivitis, asthma and dermatitis. The reasons for this increasing prevalence are unknown. The main risk factors are genetic predisposition, allergen exposure, environmental pollutants, decreased stimulation of immune system during the critical period of development and lifestyle. Allergic diseases must be treated as common health disorder. They can express themselves in any age groups and in many different organs. IgE antibody is the main connection between involved organs. Specific IgE is still being identified using the 100 years old skin testing method and quantitative immunoenzymatic method in serum. In spite of the permanent improvement of both methods, neither skin reactivity to allergens nor measurable specific IgE necessarily mean a clinically manifested disease. The interpretation of these findings is still in the clinician's domain. Allergic diseases rarely have a fatal outcome, but have a long duration. They need a complex treatment and are a substantial individual and public socio-economic burden. Studies of factors influencing the ontogeny and maturation of the immune system in the early human development as well as studies of interaction between environment and genetic predisposition will provide a new insight in the aetiology of allergic diseases. This rewiev presents curent views on the epidemiology, pathogenesis, diagnosis, therapy and prevention of allergic diseases.     

黑米花色苷提取物对大鼠抗过敏作用

目的观察黑米花色苷提取物(anthocyanin-rich extract from black rice,AEBR)的抗过敏作用并探讨其可能的作用机制。方法通过IgE诱导大鼠被动皮肤过敏反应(PCA)实验,用比色法测定黑米花色苷提取物在体内对肥大细胞影响;体外实验观察黑米花色苷提取物对IgE诱导组胺释放、细胞内钙摄入及其他炎性介子的影响。结果动物实验显示,AEBR高、中剂量组(300、150 mg/kg)明显抑制PCA实验,抑制率分别49.71%、30.40%。细胞实验显示,AEBR高、中剂量组(100、50μg/L)明显抑制组胺的释放(抑制率分别为75.56%、44.76%)、细胞内钙摄入(抑制率分别为64.75%、44.56%)以及肿瘤坏死因子-α(TNF-α)[黑米花色苷提取物(25、50、100μg/L)给药10 min使TNF-α蛋白表达分别下降7.8%、80%与85%]、白细胞介素6(IL-6)[黑米花色苷提取物(25、50、100μg/L)给药10min使IL-6蛋白表达分别下降5.6%,77%与84.1%]的释放(P<0.05)。结论黑米花色苷提取物抗过敏作用与抑制肥大细胞脱颗粒及炎性介子的...     

Environmental tobacco smoke, indoor allergens, and childhood asthma

Both environmental tobacco smoke and indoor allergens can exacerbate already established childhood albeit primarily through quite disparate mechanisms. In infancy and childhood, environmental tobacco smoke (ETS) exposure is associated with measures of decreased flow in the airways, bronchial hyperresponsiveness, and increased respiratory infections, but the relationship between ETS and allergy is poorly understood. Indoor allergens from dust mite, cockroach, and cat can be associated with asthma exacerbation in children sensitized to the specific allergens. The precise role of either ETS or indoor allergens in the development of asthma is less well understood. The strong and consistent association between ETS and asthma development in young children may relate to both prenatal and postnatal influences on airway caliber or bronchial responsiveness. Dust mite allergen levels predict asthma in children sensitized to dust mite. The tendency to develop specific IgE antibodies to allergens (sensitization) is associated with and may be preceded by the development of a T-helper (Th)2 profile of cytokine release. The importance of either ETS or indoor allergens in the differentiation of T cells into a Th2-type profile of cytokine release or in the localization of immediate-type allergic responses to the lung is unknown. This article evaluates the strength of the evidence that ETS or indoor allergens influence asthma exacerbation and asthma development in children. We also selectively review data for the effectiveness of allergen reduction in reducing asthma symptoms and present a potential research agenda regarding these two broad areas of environmental exposure and their relationship to childhood asthma.     

低剂量辐射小鼠骨髓细胞凋亡率的变化

目的:探讨低剂量射线暴露小鼠骨髓细胞凋亡率的变化及意义。方法:以Co60射线照射ICR小鼠,制备不同时间段的骨髓单个核细胞的单细胞悬液,用PI/FITC-Annexin V双染法,通过流式细胞仪检测样品的凋亡率。结果:骨髓单个核细胞早期凋亡率于照射后6 h明显增高;晚期凋亡率随辐射剂量增大而增高。白细胞计数及骨髓细胞微核率于24~30 h与对照组比较差异有显著性(P<0.05,P<0.01)。结论:小鼠骨髓细胞凋亡率的变化可及时反映射线对小鼠骨髓细胞的影响。细胞凋亡率检测可能成为低剂量射线接触人群的早期监控指标。