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1.
Chemosphere ; 243: 125404, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995871

RESUMO

Scombroid poisoning in fish-based and other food products has raised concerns due to toxicity outbreaks and incidences associated with histamine, thus measuring the amount of histamine toxic molecule is considered crucial quality indicator of food safety and human health. In this study, liposome-based measurement of histamine was performed via rupturing mechanism of sulforhodamine B dye encapsulated anti-histamine antibody conjugated liposomal nanovesicles. The immunosensing ability of immuno-liposomal format was assessed by monitoring the fluorescence at excitation/emission wavelength of 550/585 nm. Immuno-liposomal format assays were considered, one based on single wash procedure (Method 1), which had a detection limit of 10 ppb and quantification limit 15-80 ppb. While Method 2 based on one-by-one wash procedure had a detection limit of 2-3 ppb and quantification limit 8.5 ppb-200 ppm that required 2 h 30 min to perform. In view of better quantification limit, Method 2 was chosen for further tests required to validate its applicability in real samples. The feasibility of Method 2 was reconfirmed in fresh mackerel fish, and canned fish (tuna and salmon) with a similar detection limits but with low amplified fluorescence signals and sufficient levels of histamine recovery from fresh mackerel (73.50-99.98%), canned tuna (79.08-103.74%) and salmon (74.56-99.02%). The specificity and method accuracy were expressed as % CV in the range 5.34%-8.48%. Overall, the developed multi-well sensing system (Method 2) showed satisfactory specificity, cost effectiveness, rapidity, and stability for monitoring histamine toxicity as a practical food diagnostic device.


Assuntos
Imunofluorescência/métodos , Contaminação de Alimentos/análise , Histamina/análise , Toxinas Marinhas/análise , Toxinas Marinhas/envenenamento , Animais , Produtos Pesqueiros/análise , Peixes , Inocuidade dos Alimentos , Histamina/imunologia , Antagonistas dos Receptores Histamínicos , Humanos , Limite de Detecção , Lipossomos/imunologia , Rodaminas , Salmão , Alimentos Marinhos/análise , Sensibilidade e Especificidade , Atum
2.
J Agric Food Chem ; 67(43): 11911-11921, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31475818

RESUMO

Red algae sulfated polysaccharides (RASP) were extracted from Porphyra haitanensis and Gracilaria lemaneiformis. RASP were applied to effervescent tablets to develop a type of functional food, termed red algae sulfated polysaccharide effervescent tablets (RASPET), based on the antiallergic activities of RASP. The antiallergic activities and the mechanisms of RASPET were investigated in an ovalbumin (OVA)-induced mouse model of food allergy. The results revealed that RASPET alleviated intestinal villi injury by scanning electron microscopy and anaphylactic symptoms; reduced OVA-specific immunoglobulin E, histamine, and mast cell protease-1 levels in the serum; reduced the level of serum interleukin-4; increased serum interferon-γ level; and decreased B cell and mast cell populations. Remarkably, RASPET increased the levels of serum interleukin-10, transforming growth factor-ß, and upregulated splenic CD4+foxp3+ T cell populations (15.28, 16.82, and 17.58%, respectively) compared to the OVA group (13.17%). In conclusion, RASPET attenuated OVA-induced anaphylaxis via the upregulation of regulatory T cells.


Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos/administração & dosagem , Ovalbumina/efeitos adversos , Polissacarídeos/administração & dosagem , Rodófitas/química , Linfócitos T Reguladores/imunologia , Anafilaxia/etiologia , Anafilaxia/imunologia , Animais , Antialérgicos/química , Modelos Animais de Doenças , Feminino , Histamina/imunologia , Humanos , Imunoglobulina E/imunologia , Interferon gama/imunologia , Interleucina-4/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos/química , Comprimidos/administração & dosagem , Comprimidos/química
3.
Ther Umsch ; 75(1): 38-42, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31282837

RESUMO

Drug hypersensitivity in patients with presumed histamine intolerance and mast cell activation disease Abstract. There is no evidence to suggest that sensitization against drugs occurs more frequently among patients with presumed histamine intolerance compared to patients with normal tolerance to histamine. However, preclinical data suggest interactions between some drugs and histamine catabolism. Nevertheless, the clinical relevance of these findings remains unclear as histamine in humans can be catabolized by different pathways. There are no drugs for which induction or worsening of histamine intolerance has been established clinically. In patients with mastocytosis an increased rate of sensitization and specific allergies to drugs is unlikely. However, pathophysiologic understanding suggests that mast cell activation disease might enhance drug reactions, which are induced by mast cell degranulation. Additionally a possible lower threshold for unspecific mast cell degranulation in patients with mastocytosis could lead to pseudoallergic drug reactions. However an increase in the number of drug substances triggering such reactions is not expected. Nevertheless, there are lists of drug substances which are assumed to cause anaphylactic / anaphylactoid reactions especially in patients with mastocytosis. Conversely, these lists are rarely based on clinical evidence. A recently published prospective trial did not find any relevant increase of acetyl salicylic acid hypersensitivity in patients with mastocytosis. Patients with mastocytosis and a history of drug hypersensitivity should be thoroughly assessed by an allergological workup and advised to avoid triggering and / or cross reactive drug substances. We recommend that these patients avoid drugs which may interfere with the treatment of anaphylaxis like beta blockers, certain antidepressants or Catechol-O-methyltransferase inhibitors because of the increased risk for enhanced hypersensitivity reactions.


Assuntos
Hipersensibilidade a Drogas , Histamina/imunologia , Mastocitose , Catecol O-Metiltransferase , Humanos , Hipersensibilidade , Mastocitose/imunologia , Estudos Prospectivos
4.
J Agric Food Chem ; 67(22): 6313-6323, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31070910

RESUMO

Gliadins are major allergens responsible for wheat allergies. Food processing is an effective strategy to reduce the allergenicity of gluten. In the present study, we determined the secondary and tertiary structures of gluten and gliadins treated by chemical, physical, and enzymatic means through FTIR, surface hydrophobicity, intrinsic fluorescence spectra, and UV absorption spectra. The results showed that the three treatments of phosphorylation and alcalase and papain hydrolyses significantly changed the conformational structures of gliadins, especially the secondary structure. Then, the potential allergenicity of the phosphorylated and alcalase and papain hydrolyzed gliadins were further characterized, and we observed a significant decrease in the allergenicity through the results of the index of spleen, serum total IgE, gliadin-specific IgE, histamine, and serum cytokine concentrations. An elevation of Th17 cells, the absence of Treg cells, and an imbalance in Treg/Th17 are associated with allergy. On the basis of the expression levels of related cytokines and key transcription factors, we also confirmed that phosphorylation and alcalase and papain hydrolysis could effectively reduce the allergenicity of gliadins by improving the imbalance of both Th1/Th2 and Treg/Th17 in the spleens of sensitized mice. This study suggested that the changes in conformational structure contribute to gliadin hyposensitization and that phosphorylation and alcalase and papain hydrolysis may be promising strategies for the production of wheat products with low allergenicity.


Assuntos
Gliadina/química , Gliadina/imunologia , Papaína/química , Subtilisinas/química , Hipersensibilidade a Trigo/imunologia , Alérgenos/química , Alérgenos/imunologia , Animais , Biocatálise , Histamina/imunologia , Humanos , Hidrólise , Imunoglobulina E/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Baço/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Triticum/química , Triticum/imunologia
5.
J Pharm Biomed Anal ; 172: 33-41, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31022614

RESUMO

The basophil histamine release test (HRT) is an important in vitro diagnostic assay to evaluate immunoglobin E (IgE)-mediated allergic responses. In this study, a bioanalytical LC-MS/MS method was developed and validated to quantify histamine in the leukocyte suspension from human peripheral blood. The method used pre-column derivatization with phenylisothiocyanate (PITC) and the resulting phenylthiocarbamyl (PTC) histamine was analyzed by positive-ion electrospray ionization using the multiple reaction monitoring mode. Chromatographic separation was achieved using an Imtakt-HT C18 column (2.1 mm × 50 mm, 3.0 µm), with a flow rate of 0.35 mL/min, 2 µL injection, and gradient elution with a mixture of acetonitrile-2 mM ammonium acetate buffer (both containing 0.1% formic acid). The total runtime of the method was 3.0 min including equilibration time. The method had a lower limit of detection of 0.1 ng/mL, and the quantifiable range was 0.1-100 ng/mL in the leukocyte suspension. The intra-day and inter-day precision and accuracy results were within the acceptable limits. It was established that histamine quantification should be performed within 2 h of preparing the leukocyte suspension, and freezing and thawing should be avoided. This method was successfully applied to the diagnosis and evaluation of the pathophysiologic mechanism of respiratory or cutaneous allergic diseases.


Assuntos
Coleta de Amostras Sanguíneas/métodos , Histamina/sangue , Hipersensibilidade/diagnóstico , Cromatografia Líquida de Alta Pressão/métodos , Histamina/imunologia , Humanos , Hipersensibilidade/sangue , Hipersensibilidade/imunologia , Leucócitos/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos
7.
Int Immunopharmacol ; 72: 1-11, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30953868

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by Diagnosis and Statistic Manual 5 (DSM-5) as persistent social interaction and communication deficient across multiple contexts. Various immunological findings have been reported in children with ASD, and co-existing allergic problems have been recorded in children diagnosed with ASD. Osthole, the effective component of Chinese traditional medicine, is reported to have anti-inflammatory effects. This study assessed the anti-inflammatory effect of osthole on the histamine-induced inflammatory responses in PBMC cells. METHODS: Peripheral blood mononuclear cells (PBMC's) from children with: (1) ASD group with co-existing allergies/asthma (n = 29); (2) ASD group without allergy/asthma (n = 29); (3) Allergy group (n = 30) and from typically developing age-matched control subjects (n = 28) were stimulated with either histamine, FXF, osthole or mixture of this substances. mRNA COX-2 gene expression, COX-2 production and inhibitory effect of tested substances on COX-2 were assessed after stimulation. RESULTS: Children with ASD may show either an innate proinflammatory response or increased activity of COX-2 which could display more impaired behavioral profile than children with non-inflamed. This study indicated that COX-2 may be involved in pathogenesis of ASD and/or allergy, and osthole could be used to decrease the effects of COX-2 in inflammation and ASD development. High incidence of allergy in ASD patients may indicate immune dysregulation that could be of relevance to the pathophysiology, symptomatology or neuroimmunology of ASD. CONCLUSIONS: This study shows that fexofenadine (FXF - antihistamine drug) and osthole exhibit selective COX-2 enzyme inhibitory activity. The selective COX-2 activity of osthole may explain further the anti-inflammatory properties of osthole in relieving congestion in allergic rhinitis, and as distinctive effects between FXF and osthole were observed, individual antihistamines may have different modes of action via the COX enzyme system.


Assuntos
Anti-Inflamatórios/farmacologia , Transtorno do Espectro Autista/imunologia , Cumarínicos/farmacologia , Hipersensibilidade/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Criança , Pré-Escolar , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Histamina/imunologia , Antagonistas dos Receptores Histamínicos/farmacologia , Humanos , Hipersensibilidade/genética , Hipersensibilidade/metabolismo , Lactente , Leucócitos Mononucleares/imunologia , Masculino , Terfenadina/análogos & derivados , Terfenadina/farmacologia
8.
Int Immunopharmacol ; 72: 284-291, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31005038

RESUMO

Imiquimod (Imiq) is a synthetic imizoquinoline compound which can act on Toll-like receptor (TLR)7 and transduce signals involved in cell activation. We investigated the role of Imiq on contact hypersensitivity (CHS) and explored the potential mechanisms of mast cells involved in the process. Topical application of Imiq cream augmented DNFB mediated CHS in C57BL/6 mice. Imiq application induced skin inflammation and increased the number of dendritic cells (DCs) in the draining lymph nodes (DLNs). The splenic cell proliferation to DNBS in DNFB and Imiq treated mice was greater than that in mice of DNFB treatment alone. Peritoneal cell-derived mast cells (PCMCs) expressed TLR7 mRNA. The results from toluidine blue staining for mast cells and histamine detection indicated that Imiq alone did not induce mast cell degranulation while Imiq plus DNFB significantly induced mast cell degranulation. Cromolyn, pyrilamine and cimetidine attenuated CHS reaction induced by Imiq. Our findings suggest that Imiq could augment the intensity of CHS reaction. The mechanisms underlying the effect may relate to histamine release by mast cells and induction of DC homing to DLNs. Blocking histamine action in early time of allergen contact is beneficial to the alleviation of CHS.


Assuntos
Adjuvantes Imunológicos/toxicidade , Células Dendríticas/efeitos dos fármacos , Dermatite de Contato/imunologia , Histamina/imunologia , Imiquimode/toxicidade , Mastócitos/efeitos dos fármacos , Administração Tópica , Animais , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/imunologia , Dinitrofluorbenzeno , Feminino , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Mastócitos/imunologia , Camundongos Endogâmicos C57BL , Baço/citologia
9.
Food Funct ; 10(4): 2030-2039, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30907398

RESUMO

Resveratrol exists widely in plant species and has a variety of anti-oxidant, anti-inflammatory, and immunomodulatory properties. However, there have been few reports regarding its anti-food allergic activity. In this study, we demonstrated that resveratrol (isolated from Abies georgei) could decrease the release of ß-hexosaminidase and histamine in rat basophilic leukemia-2H3 cells. Resveratrol was not only found to suppress the development of diarrhea, up-regulate the rectal temperature of ovalbumin-allergic mice, and decrease the serum level of specific immunoglobulin E, mouse mast cell protease-1 and histamine, but also found to decrease the population of dendritic cells, B cells and mast cells of ovalbumin -allergic mice in the spleen or mesenteric lymph node. Furthermore, resveratrol inhibited the release of ß-hexosaminidase and histamine in bone marrow-derived cells and alleviated mast cell-mediated passive cutaneous anaphylaxis reactions. These findings indicated that resveratrol isolated from Abies georgei might have the potential to alleviate food hypersensitivity or allergic disease.


Assuntos
Abies/química , Antialérgicos/administração & dosagem , Hipersensibilidade Alimentar/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Resveratrol/administração & dosagem , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linhagem Celular , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/imunologia , Histamina/imunologia , Humanos , Imunoglobulina E/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Peptídeo Hidrolases/imunologia , Ratos , beta-N-Acetil-Hexosaminidases/imunologia
10.
Pediatr Neonatol ; 60(2): 172-177, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29983339

RESUMO

BACKGROUND: To investigate the association between histamine skin reactivity and body mass index (BMI) and other clinical factors, 526 children (3-6 years old) who underwent a skin-prick test (SPT) to diagnose allergic rhinitis were enrolled. METHODS: The SPT was carried out using 43 common allergens (commercial kit). The wheal size was analyzed. The associations between histamine reactivity and age, gender, BMI, atopy, parental smoking history, and testing season were examined. RESULTS: Mean age was 4.6 ± 1.1 years. Among all 526 children, 202 (38.4%) had intermittent allergic rhinitis (IAR), 164 (32.1%) had IAR + persistent allergic rhinitis (PER), and 160 (30.4%) had PER. The size of the histamine skin wheal and maximum diameter for positive allergens showed significant seasonal differences (P = 0.001 and P = 0.02, respectively). Children with biparental allergy history had a higher BMI (P = 0.006). BMI (P < 0.001), summer testing (P = 0.001), and autumn testing (P < 0.001) were independently associated with the size of the histamine skin wheal. Only winter testing was independently associated with the maximal diameter for positive allergens (P = 0.002). CONCLUSIONS: Higher histamine skin reactivity was associated with higher BMI and summer or autumn testing. Subject BMI and season should be considered for better interpretation of the SPT. The mechanisms underlying these associations require further study.


Assuntos
Índice de Massa Corporal , Histamina/imunologia , Rinite Alérgica/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Rinite Alérgica/imunologia , Estações do Ano , Testes Cutâneos
11.
BMC Gastroenterol ; 20(1): 2, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31892312

RESUMO

BACKGROUND: The aim of this study was to investigate the efficacy and safety of the novel complex drug, consisting of released-active form of antibodies to S-100 protein, tumor necrosis factor-α and histamine, (Kolofort) under outpatient conditions in patients with functional dyspepsia (FD), irritable bowel syndrome (IBS), and FD-IBS overlap. METHODS: The subjects of the observational noninterventional retrospective program were the data of 14,362 outpatient records of patients with diagnosed FD, IBS, and/or overlap, who were observed by gastroenterologists from November 01, 2017, through March 30, 2018, who received the drug Kolofort in monotherapy for 12 weeks, 2 tablets twice a day. To assess the presence and severity of symptoms of functional gastrointestinal disorders (FGID), the "7*7" questionnaire developed by a working group from the Russian Gastroenterological Association was used. The evaluated parameters included the proportion of patients: who had a 50% or more reduction in the total score; who have switched to the less severe category of the condition; who have switched to the "healthy" or "borderline ill" severity categories; and the change in the score in domains 1-7. RESULTS: The final efficacy analysis included data from 9254 patients. A decrease in the total score by 50% or more was observed in 80.45% of patients with FD, 79.02% of patients with IBS, and in 83% of patients with both IBS and FD. Switch to a lower severity category of the condition at the end of therapy was noted in 93.35% of patients with FD, in 93.80% of cases in patients with IBS, and in 96.17% of cases in patients with a combination of IBS and FD. A total of 94 adverse events (AEs) were reported in 80 patients (0.65%). CONCLUSION: The COMFORT program has demonstrated the positive effect of treatment in the majority of patients with IBS and FD and their combination in real clinical practice.


Assuntos
Anticorpos/uso terapêutico , Dispepsia/terapia , Histamina/imunologia , Imunoterapia/métodos , Síndrome do Intestino Irritável/terapia , Proteínas S100/imunologia , Fator de Necrose Tumoral alfa/imunologia , Adulto , Assistência Ambulatorial , Anticorpos/efeitos adversos , Combinação de Medicamentos , Dispepsia/complicações , Feminino , Inquéritos Epidemiológicos/instrumentação , Humanos , Imunoterapia/efeitos adversos , Síndrome do Intestino Irritável/complicações , Masculino , Estudos Retrospectivos , Federação Russa , Índice de Gravidade de Doença , Avaliação de Sintomas/métodos , Resultado do Tratamento
12.
Front Immunol ; 9: 2119, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319608

RESUMO

Our previous in vitro studies revealed that histamine via histamine the H4-receptors (H4R), as compared to other stimuli, such as eotaxin or formylpeptides, rather partially activates eosinophilic granulocytes (eosinophils). In order to evaluate the H4R-mediated activation of eosinophils in vivo, we employed dextran sodium sulfate (DSS)-induced colitis in mice, closely resembling human ulcerative colitis (UC), which is largely characterized by a local eosinophilic infiltration of the colon. IL-5-deficient BALB/c mice served as a model with reduced endogenous numbers of eosinophils, in which wild-type (H4R+/+) or H4R-deficient (H4R-/-) eosinophils were adoptively transferred during the course of DSS-induced colitis. During the 1-week observation period, transfer of eosinophils transiently reversed the acute clinical colitis-like phenotype (body weight loss, perianal bleeding, soft stool consistency) resulting from IL-5-deficiency. This reversion was significantly more pronounced upon transfer of eosinophils from H4R+/+ mice as compared to those from H4R-/- mice. Already at the end of the observation period, the clinical effects of the transfer of H4R+/+ and H4R-/- eosinophils became similar, as were the results of the histological examination of the cola and the analyses of cytokine production in cola and in re-stimulated lymph node cells performed at this time. Thus, analyzing clinical and pathological parameters representative of colitis in this model, we demonstrate that as well as in vitro, also in vivo histamine via the H4R only partially activates eosinophils.


Assuntos
Colite Ulcerativa/imunologia , Eosinófilos/imunologia , Histamina/imunologia , Receptores Histamínicos H4/imunologia , Transferência Adotiva , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/citologia , Colo/imunologia , Colo/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Eosinófilos/transplante , Histamina/metabolismo , Humanos , Interleucina-5/deficiência , Interleucina-5/genética , Interleucina-5/imunologia , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Histamínicos H4/genética , Receptores Histamínicos H4/metabolismo , Células Th2/imunologia
13.
Cell Immunol ; 332: 121-128, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30121125

RESUMO

BACKGROUND: Mivacurium is a non-depolarizing muscle relaxant and widely used as a short-acting anesthetic. Pseudo-allergic reactions to mivacurium occur when it is administered during perioperative anesthesia. These reactions may present a serious threat to the patient's life, particularly in children. METHODS: MAS-related G protein coupled receptor-related pseudo-allergic reactions that were induced by mivacurium were investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. RESULTS: Mivacurium caused pseudo-allergic reactions in wild-type mice by inducing mast cells to release histamine. However, it did not induce a similar phenomenon in KitW-sh/W-sh mice. Furthermore, MrgprB2-knockout mice displayed no inflammatory response to mivacurium. Mivacurium induced LAD2 cell degranulation in a dose-dependent manner. Mivacurium stimulated intracellular calcium ion (Ca2+) influx in MRGPRX2-HEK293 cells but not in NC-HEK293 cells. However, mivacurium induced the release of only low levels of mediators in LAD2 cells transfected with MRGPRX2-targeted small interfering (si)RNA. Notably, cytokine release was not observed in LAD2 cells even when stimulated with high concentrations of mivacurium. CONCLUSION: Mivacurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. However, mivacurium did not induce the release of other cytokines. Therefore, the targeting of MRGPRX2 can potentially block mivacurium-induced adverse drug effects, particularly pseudo-allergic reactions.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Mastócitos/efeitos dos fármacos , Mivacúrio/efeitos adversos , Mivacúrio/imunologia , Receptores Acoplados a Proteínas-G/imunologia , Anafilaxia/imunologia , Animais , Cálcio/imunologia , Degranulação Celular/imunologia , Linhagem Celular , Citocinas/imunologia , Células HEK293 , Histamina/imunologia , Humanos , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
15.
Curr Opin Allergy Clin Immunol ; 18(5): 370-376, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30048251

RESUMO

PURPOSE OF REVIEW: The aim of the review is to describe the different clinical pictures of anaphylaxis (phenotypes), in relation to the underlying mechanisms and potential biomarkers, to describe anaphylaxis endotypes. This may aid in achieving a better understanding, management and outcomes of such severe reactions. RECENT FINDINGS: Different anaphylaxis phenotypes have been outlined, ranging from the classical type-I-like to those suggestive of cytokine-storm-like or complement-mediated reactions. Underlying mechanisms differ and biomarkers of cells and systems involved are being identified (tryptase, IL-6, bradykinin etc.) SUMMARY: Identifying specific phenotypes/endotypes will allow the application of precision medicine in patients with anaphylaxis, providing insights to the most appropriate approach in each case.


Assuntos
Anafilaxia/imunologia , Biomarcadores/metabolismo , Ativação do Complemento/imunologia , Citocinas/imunologia , Fenótipo , Anafilaxia/metabolismo , Basófilos/imunologia , Bradicinina/imunologia , Bradicinina/metabolismo , Carboxipeptidases A/imunologia , Carboxipeptidases A/metabolismo , Quimases/imunologia , Quimases/metabolismo , Citocinas/metabolismo , Histamina/imunologia , Histamina/metabolismo , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Interleucina-6/imunologia , Interleucina-6/metabolismo , Mastócitos/imunologia , Fator de Ativação de Plaquetas/imunologia , Fator de Ativação de Plaquetas/metabolismo , Medicina de Precisão , Triptases/imunologia , Triptases/metabolismo
16.
Proc Natl Acad Sci U S A ; 115(25): 6434-6439, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29866844

RESUMO

BP180, also known as collagen XVII, is a hemidesmosomal component and plays a key role in maintaining skin dermal/epidermal adhesion. Dysfunction of BP180, either through genetic mutations in junctional epidermolysis bullosa (JEB) or autoantibody insult in bullous pemphigoid (BP), leads to subepidermal blistering accompanied by skin inflammation. However, whether BP180 is involved in skin inflammation remains unknown. To address this question, we generated a BP180-dysfunctional mouse strain and found that mice lacking functional BP180 (termed ΔNC16A) developed spontaneous skin inflammatory disease, characterized by severe itch, defective skin barrier, infiltrating immune cells, elevated serum IgE levels, and increased expression of thymic stromal lymphopoietin (TSLP). Severe itch is independent of adaptive immunity and histamine, but dependent on increased expression of TSLP by keratinocytes. In addition, a high TSLP expression is detected in BP patients. Our data provide direct evidence showing that BP180 regulates skin inflammation independently of adaptive immunity, and BP180 dysfunction leads to a TSLP-mediated itch. The newly developed mouse strain could be a model for elucidation of disease mechanisms and development of novel therapeutic strategies for skin inflammation and BP180-related skin conditions.


Assuntos
Autoantígenos/metabolismo , Inflamação/metabolismo , Colágenos não Fibrilares/metabolismo , Pele/metabolismo , Imunidade Adaptativa/imunologia , Animais , Autoantígenos/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Histamina/imunologia , Histamina/metabolismo , Humanos , Imunoglobulina E/sangue , Inflamação/sangue , Inflamação/imunologia , Queratinócitos/imunologia , Queratinócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/metabolismo , Prurido/sangue , Prurido/imunologia , Prurido/metabolismo , Pele/imunologia
17.
Eur J Pharmacol ; 833: 124-130, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29859836

RESUMO

Galectin-1 (Gal-1) is a ß-galactoside-binding protein with diverse biological activities in the pathogenesis of inflammation, however the mechanisms by which Gal-1 modulates cellular responses in allergic inflammatory processes have not been fully determined. In this study, we evaluated the therapeutic potential of Gal-1 eye drops in an experimental model of conjunctivitis. Wistar rats received a topical application of compound (C)48/80 (100 mg/ml) into right eyes and a drop of vehicle into the contralateral eye. Another group of rats received Gal-1 (0.3 or 3 µg/eye) or sodium cromoglycate (SCG; 40 mg/ml) in both eyes and, after 15 min, right eye was challenged with C48/80. Conjunctivitis-induced by C48/80 was characterized by severe eyelid oedema and tearing, but clinical signs were ameliorated by eye drop doses of both Gal-1 (0.3/3 µg) and SCG. As expected, an increased proportion of degranulated mast cells (62%, P < 0.01) and lower histamine levels were observed after 6 h of C48/80 challenge, compared to control (32%). This effect was abrogated by Gal-1 and SCG, which reduced mast cell degranulation (31-36%), eosinophil migration and eosinophil peroxidase levels in the eyes. Gal-1 (3 µg) and SCG treatments also decreased IL-4 levels, as well as activation of mitogen activated protein kinases compared to untreated C48/80 eyes. Our findings suggest that Gal-1 eye drops represent a new therapeutic strategy for ocular allergic inflammation.


Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Conjuntivite Alérgica/tratamento farmacológico , Galectina 1/uso terapêutico , Animais , Antialérgicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Degranulação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Conjuntivite Alérgica/induzido quimicamente , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/patologia , Citocinas/imunologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/enzimologia , Eosinófilos/fisiologia , Olho/efeitos dos fármacos , Olho/imunologia , Olho/patologia , Galectina 1/administração & dosagem , Histamina/imunologia , Mastócitos/efeitos dos fármacos , Mastócitos/fisiologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , Soluções Oftálmicas , Peroxidases/metabolismo , Ratos Wistar , p-Metoxi-N-metilfenetilamina
18.
Lab Invest ; 98(8): 1039-1051, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29765110

RESUMO

Enterovirus (EV) 71 infection has been widely acknowledged as the leading cause of severe hand, foot and mouth disease (HFMD), which may rapidly lead to fatal pulmonary edema. In this study, we established a mouse model for EV71 infection exhibiting high incidence of severe symptoms with pulmonary edema. Mast cells (MCs) accumulation, activation and allergic inflammation were found in the brains, lungs and skeletal muscle of mice after EV71 infection, especially in the lungs of mice. Levels of histamine, platelet-activating factor (PAF), interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor-α (TNF-α), nitric oxide (NO), endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and noradrenaline (NA) were increased in EV71-infected lungs. In addition, EV71 infection reduced the number of pulmonary T cells, dendritic cells (DCs) and monocytes, and increased the number of lung eosinophils, Tregs and MCs. MCs number and tryptase expression in target organs or tissues posed a trend towards an increase from control to severe mice. There were positive correlations between MCs number in the brains (r = 0.701, P = 0.003), lungs (r = 0.802, P < 0.0001), skeletal muscles (r = 0.737, P = 0.001) and mean clinical score. Thus, our results suggested that MCs contributed to the pulmonary edema during EV71 infection.


Assuntos
Enterovirus Humano A/imunologia , Infecções por Enterovirus/imunologia , Mastócitos/imunologia , Edema Pulmonar/imunologia , Animais , Animais Recém-Nascidos , Encéfalo/imunologia , Encéfalo/metabolismo , Encéfalo/virologia , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/metabolismo , Infecções por Enterovirus/virologia , Histamina/imunologia , Histamina/metabolismo , Humanos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/virologia , Mastócitos/metabolismo , Mastócitos/virologia , Camundongos Endogâmicos BALB C , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Músculo Esquelético/virologia , Edema Pulmonar/metabolismo , Edema Pulmonar/virologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
J Agric Food Chem ; 66(22): 5581-5592, 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29763312

RESUMO

Deep-sea-derived butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.


Assuntos
4-Butirolactona/análogos & derivados , Anafilaxia/tratamento farmacológico , Aspergillus/química , Hipersensibilidade Alimentar/tratamento farmacológico , Mastócitos/imunologia , 4-Butirolactona/administração & dosagem , Anafilaxia/genética , Anafilaxia/imunologia , Animais , Aspergillus/genética , Aspergillus/isolamento & purificação , Células Cultivadas , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Histamina/imunologia , Humanos , Imunoglobulina E/imunologia , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/imunologia , Água do Mar/microbiologia
20.
Cell Physiol Biochem ; 46(6): 2401-2411, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29742501

RESUMO

BACKGROUND/AIMS: As a major inflammatory molecule released from mast cell activation, histamine has been reported to regulate TLRs expression and cytokine production in inflammatory cells present in the microenvironment. In this study, we determined the ability of histamine to modulate TLRs expression and cytokine production in mast cells. METHODS: HMC-1 and P815 cells were exposed to various concentrations of histamine in the presence or absence of histamine antagonist for 2, 6 or 16 h. The effect of histamine on the expression of TLR3 protein and mRNA was analyzed by flow cytometry、 RT-PCR and immunofluorescent microscopy. Furthermore, we also examined the effect of histamine on the secretion of MCP-1 and IL-13 from mast cells by ELISA. RESULTS: The amplification of TLR3 mRNA and protein expression in mast cells was observed after incubation with histamine, which was accompanied by increasing secretion of IL-13 and MCP-1 via H1 receptor. The signaling pathways of PI3K/ Akt and Erk1/2/MAPK contributed to these induction effects. CONCLUSION: These results demonstrate that histamine up-regulates the expression of TLR3 and secretion of IL-13 and MCP-1 in mast cells, thus identifying a new mechanism for the histamine inducing allergic response.


Assuntos
Histamina/imunologia , Interleucina-13/imunologia , Mastócitos/imunologia , Receptor 3 Toll-Like/genética , Regulação para Cima , Animais , Linhagem Celular , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Mastócitos/metabolismo , Camundongos , RNA Mensageiro/genética , Receptor 3 Toll-Like/imunologia
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