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1.
Immunol Allergy Clin North Am ; 42(1): 45-63, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34823750

RESUMO

There is strong evidence of an association between severe anaphylaxis, especially hymenoptera venom induced, and mast cell (MC) disorders. It has been thought that intrinsic abnormalities in MCs, including the presence of the activating KIT D816V mutation in mastocytosis or of genetic trait, hereditary alpha-tryptasemia, may influence susceptibility to severe anaphylaxis. This article evaluates the potential mechanisms leading to severe MC activation, as well as the differential diagnosis of and range of symptoms attributable to MC mediator release. Also, we offer a global classification for disorders related to MC activation.


Assuntos
Anafilaxia , Venenos de Artrópodes , Mastocitose , Anafilaxia/diagnóstico , Anafilaxia/etiologia , Humanos , Mastócitos , Mastocitose/diagnóstico , Triptases
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120331, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536894

RESUMO

Both electroporation-assisted and ultrasound-assisted delivery methods can rapidly deliver nanoparticles into living cells for surface-enhanced Raman scattering (SERS) detection, but these two methods have never been compared. In this study, electroporation-assisted SERS and ultrasound-assisted SERS were employed to detect the biochemical changes of degranulated mast cells induced by mast cell stimulator (C48/80). The results showed that the cell damage of electroporation based on controllable electric pulse was smaller than that of ultrasound based on cavitation. Transmission electron microscope images of cells indicated that the nanoparticles delivered by electroporation were mainly distributed in the cytoplasm, while ultrasound could transport nanoparticles to the cytoplasm and nucleus. Therefore, electroporation-assisted SERS mainly detects the biochemical information of cytoplasm, while ultrasound-assisted SERS gets more spectral signals of nucleic acid. Both methods can obtain high quality SERS signal of cells. With drug treatment, the SERS peak intensity of 733 cm-1 attributed to phosphatidylserine decreased significantly, which may be due to the activation of mast cell degranulation pathway stimulated by C48/80 agonist, resulting in a large amount of intracellular serine being used to synthesize tryptase, while the production of phosphatidylserine decreased. Further, based on principal component analysis and linear discriminant analysis (PCA-LDA approach), ultrasound-assisted SERS could achieve better sensitivity, specificity and accuracy in the discrimination and identification of drug-treated degranulated mast cells than electroporation assisted SERS. This exploratory work is helpful to realize the real-time dynamic SERS detection of intracellular biochemical components, and it also has great potential in intracellular SERS analysis, such as the cytotoxicity assay of anti-tumor drugs or cancer cell screening.


Assuntos
Mastócitos , Nanopartículas Metálicas , Análise Discriminante , Eletroporação , Análise de Componente Principal , Análise Espectral Raman
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(12): 1073-1078, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34906294

RESUMO

Objective To investigate the role of mast cell activation products in promoting angiogenesis. Methods SD rat peritoneal mast cells (RPMC) were isolated and activated by calcium ionophore. The activation products were extracted and the activity of chymase was detected. Thirty BALB/c mice were randomly divided into a control group, an activation product group, and an inhibitor group (10 mice in each group), and the angiogenisis of mast cell activation products was studied by matrigel plug assay. In the matrigel plug, the hemoglobin (Hb) concentration was determined by hemiglobincyanide (HiCN) method, the distribution of blood vessels was observed by HE staining, and the microvessel density (MVD) was detected by CD34 immunohistochemical staining. Results The activity of chymase was detected in the activation products of isolated RPMCs. The results of mice matrigel plug assay showed that the Hb level in matrigel plug of the activation product group was about 7 times higher than that of the control group, while the Hb level of the inhibitor group was 80.8% lower than that of the activation product group. HE staining showed new blood vessels in the matrigel plug of the activation product group, and some vascular lumens were observed. The results of MVD showed that the MVD in matrigel plug of the activation product group was about 5 times than that of the control group, while MVD of the inhibitor group was 66.2% lower than that of the activation product group. Conclusion Chymase, a product of mast cell activation, is the main mediator to promote angiogenesis in mouse matrigel plugs.


Assuntos
Mastócitos , Animais , Quimases , Colágeno , Combinação de Medicamentos , Laminina , Camundongos , Camundongos Endogâmicos BALB C , Proteoglicanas , Ratos , Ratos Sprague-Dawley
5.
Zhonghua Yu Fang Yi Xue Za Zhi ; 55(12): 1513-1517, 2021 Dec 06.
Artigo em Chinês | MEDLINE | ID: mdl-34963253

RESUMO

Mast cells are the main effector cells in allergic diseases. Allergic diseases are mostly a direct result of mast cell mediator release effects, while allergen activation is only one of many triggers for mast cell mediator secretion. Increased mast cell number, high mast cell reactivity, or both can lead to abnormal mast cell activation. Mast cell activated syndrome (MCAS) refers to a group or a"spectrum"of mediator-related, symptomatically similar diseases in which mast cells are stimulated by multiple factors. The symptoms and signs of mast cell disease overlap with allergic diseases, but the etiology is different, which requires clinical attention. This article summarizes the research progress on mast cell activation syndrome in recent years thus increase awareness of the differential diagnosis.


Assuntos
Mastocitose , Humanos , Mastócitos
6.
Signal Transduct Target Ther ; 6(1): 428, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34921131

RESUMO

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. In this study, we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation altered various signaling pathways in alveolar epithelial cells, particularly, the induction of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.


Assuntos
COVID-19/metabolismo , Degranulação Celular , Lesão Pulmonar/metabolismo , Mastócitos/metabolismo , Alvéolos Pulmonares/metabolismo , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/genética , Linhagem Celular Tumoral , Feminino , Humanos , Lesão Pulmonar/genética , Lesão Pulmonar/virologia , Macaca mulatta , Masculino , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Alvéolos Pulmonares/virologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
7.
Rev Med Interne ; 42(12): 869-874, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34776279

RESUMO

Hymenoptera venom anaphylaxis is the most frequent cause of anaphylaxis and responsible for about 20% of all fatal anaphylaxis cases in adults. We report two cases of fatal hymenoptera venom anaphylaxis with undiagnosed underlying mastocytosis and review the risk factors for severe or fatal hymenoptera venom anaphylaxis, as well as the specificities of its association with mastocytosis. As hymenoptera venom allergic patients with underlying clonal mast cell disorder generally lack typical skin lesions of mastocytosis, its diagnosis can easily be missed, underscoring the importance and need for diagnostic strategies in order to correctly identify these patients. Predominant cardiovascular symptoms in the absence of urticaria or angioedema following an insect sting are suggestive of underlying clonal mast cell disorder, and should be distinguished from panic attack or vasovagal syncope. Similarly, an unexplained syncope or an "idiopathic" anaphylaxis might reveal mastocytosis or hereditary alpha-tryptasemia. Acute and basal serum tryptase measurements should always be integrated in the diagnostic work-up of an insect sting reaction or unexplained syncope or shock of any origin.


Assuntos
Anafilaxia , Venenos de Artrópodes , Himenópteros , Mastocitose , Anafilaxia/diagnóstico , Animais , Humanos , Mastócitos , Mastocitose/complicações , Mastocitose/diagnóstico , Triptases
8.
Int J Mol Sci ; 22(21)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34768820

RESUMO

Disseminated intravascular coagulation (DIC) is a severe condition characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. In the last years, it represents one of the most frequent consequences of coronavirus disease 2019 (COVID-19). The pathogenesis of DIC is complex, with cross-talk between the coagulant and inflammatory pathways. The objective of this study is to investigate the anti-inflammatory action of ultramicronized palmitoylethanolamide (um-PEA) in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by continual infusion of LPS (30 mg/kg) for 4 h through the tail vein. Um-PEA (30 mg/kg) was given orally 30 min before and 1 h after the start of intravenous infusion of LPS. Results showed that um-PEA reduced alteration of coagulation markers, as well as proinflammatory cytokine release in plasma and lung samples, induced by LPS infusion. Furthermore, um-PEA also has the effect of preventing the formation of fibrin deposition and lung damage. Moreover, um-PEA was able to reduce the number of mast cells (MCs) and the release of its serine proteases, which are also necessary for SARS-CoV-2 infection. These results suggest that um-PEA could be considered as a potential therapeutic approach in the management of DIC and in clinical implications associated to coagulopathy and lung dysfunction, such as COVID-19.


Assuntos
Amidas/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Intravascular Disseminada/tratamento farmacológico , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Sepse/complicações , Amidas/química , Amidas/farmacologia , Animais , Transtornos da Coagulação Sanguínea/etiologia , COVID-19/patologia , COVID-19/virologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Coagulação Intravascular Disseminada/etiologia , Etanolaminas/química , Etanolaminas/farmacologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão/metabolismo , Pulmão/patologia , Masculino , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Ácidos Palmíticos/química , Ácidos Palmíticos/farmacologia , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ratos , Ratos Sprague-Dawley , SARS-CoV-2/isolamento & purificação , Sepse/patologia , Serina Proteases/metabolismo
9.
Nanoscale ; 13(45): 19023-19037, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34755752

RESUMO

Multimodal gadolinium fluoride nanoparticles belong to potential contrast agents useful for bimodal optical fluorescence and magnetic resonance imaging. However, the metallic nature of the nanoparticles, similarly to some paramagnetic iron oxides, might induce allergic and anaphylactic reactions in patients after administration. A reduction of these adverse side effects is a priority for the safe application of the nanoparticles. Herein, we prepared paramagnetic poly(4-styrenesulfonic acid-co-maleic acid) (PSSMA)-stabilized GdF3 nanoparticles with surface modified by Atto 488-labeled poly(styrene-grad-2-dimethylaminoethyl acrylate)-block-poly(2-dimethylaminoethyl acrylate) (PSDA-A488) with reactive amino groups for introduction of an additional imaging (luminescence) modality and possible targeting of anticancer drugs. The saturation magnetization of GdF3@PSSMA particles according to SQUID magnetometry reached 157 Am2 kg-1 at 2 K and magnetic field of 7 T. GdF3@PSSMA-PSDA-A488 nanoparticles were well tolerated by human cervical adenocarcinoma (HeLa), mouse bone marrow-derived mast cells (BMMC), and rat basophilic mast cells (RBL-2H3); the particles also affected cell morphology and protein tyrosine phosphorylation in mast cells. Moreover, the nanoparticles interfered with the activation of mast cells by multivalent antigens and inhibited calcium mobilization and cell degranulation. These findings show that the new multimodal GdF3-based nanoparticles possess properties useful for various imaging methods and might minimize mast cell degranulation incurred after future nanoparticle diagnostic administration.


Assuntos
Mastócitos , Nanopartículas , Animais , Degranulação Celular , Fator 3 de Diferenciação de Crescimento , Humanos , Camundongos , Polímeros , Ratos
10.
J Immunol ; 207(11): 2637-2648, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34732470

RESUMO

Mast cells are important effector cells in the immune system and undergo activation (i.e., degranulation) by two major mechanisms: IgE-mediated and non-IgE-mediated mechanisms. Although IgE-mediated degranulation is well researched, the cellular mechanisms of non-IgE-mediated mast cell activation are poorly understood despite the potential to induce similar pathophysiological effects. To better understand non-IgE mast cell degranulation, we characterized and compared cellular metabolic shifts across several mechanisms of degranulation (allergen-induced [IgE-mediated], 20 nm of silver nanoparticle-mediated [non-IgE], and compound 48/80-mediated [non-IgE]) in murine bone marrow-derived mast cells. All treatments differentially impacted mitochondrial activity and glucose uptake, suggesting diverging metabolic pathways between IgE- and non-IgE-mediated degranulation. Non-IgE treatments depleted mast cells' glycolytic reserve, and compound 48/80 further inhibited the ability to maximize mitochondrial respiration. This cellular reprogramming may be indicative of a stress response with non-IgE treatments. Neither of these outcomes occurred with IgE-mediated degranulation, hinting at a separate programmed response. Fuel flexibility between the three primary mitochondrial nutrient sources was also eliminated in activated cells and this was most significant in non-IgE-mediated degranulation. Lastly, metabolomics analysis of bone marrow-derived mast cells following degranulation was used to compare general metabolite profiles related to energetic pathways. IgE-mediated degranulation upregulated metabolite concentrations for the TCA cycle and glycolysis compared with other treatments. In conclusion, mast cell metabolism varies significantly between IgE- and non-IgE-mediated degranulation suggesting novel cell regulatory mechanisms are potentially driving unexplored pathways of mast cell degranulation.


Assuntos
Imunoglobulina E/metabolismo , Mastócitos/metabolismo , Animais , Células Cultivadas , Imunoglobulina E/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL
11.
Immunol Allergy Clin North Am ; 41(4): 627-638, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34602233

RESUMO

Anaphylaxis is an acute, potentially life-threatening systemic hypersensitivity reaction. Classically, anaphylaxis is an immunoglobulin (Ig) E-mediated reaction; however, IgG or immune complex complement-related immunologic reactions that lead to degranulation of mast cells can also cause anaphylaxis. Food allergy is the most common cause of anaphylaxis, followed by drugs. Patients with anaphylaxis commonly present with symptoms involving skin or mucous membranes, followed by respiratory and gastrointestinal symptoms. Epinephrine is the drug of choice for treating anaphylaxis. Patients and caregivers should be educated on the use of epinephrine autoinjectors with periodic review of symptoms and emergency action plan for anaphylaxis.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Adolescente , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Anafilaxia/epidemiologia , Criança , Epinefrina/uso terapêutico , Hipersensibilidade Alimentar/diagnóstico , Humanos , Imunoglobulina E , Mastócitos
12.
Acta Derm Venereol ; 101(10): adv00583, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34642766

RESUMO

Pruritus can be defined as an unpleasant sensation that evokes a desire to scratch and significantly impairs patients' quality of life. Pruritus is widely observed in many dermatoses, including mastocytosis, a rare disease characterized by abnormal accumulation of mast cells, which can involve skin, bone marrow, and other organs. Increasing evidence highlights the role of mast cells in neurogenic inflammation and itching. Mast cells release various pruritogenic mediators, initiating subsequent mutual communication with specific nociceptors on sensory nerve fibres. Among important mediators released by mast cells that induce pruritus, one can distinguish histamine, serotonin, proteases, as well as various cytokines. During neuronal-induced inflammation, mast cells may respond to numerous mediators, including neuropeptides, such as substance P, neurokinin A, calcitonin gene-related peptide, endothelin 1, and nerve growth factor. Currently, treatment of pruritus in mastocytosis is focused on alleviating the effects of mediators secreted by mast cells. However, a deeper understanding of the intricacies of the neurobiology of this disease could help to provide better treatment options for patients.


Assuntos
Mastócitos , Mastocitose , Humanos , Mastocitose/diagnóstico , Prurido/diagnóstico , Prurido/etiologia , Qualidade de Vida , Pele
14.
Cancer Treat Res ; 181: 167-178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34626361

RESUMO

Mastocytosis is a rare hematologic disorder characterized by abnormal proliferation and accumulation of neoplastic mast cells in various body sites. Isolated skin involvement is termed cutaneous mastocytosis (CM) and the term systemic mastocytosis (SM) refers to multi-organ involvement, most commonly of the bone marrow, skin, liver, and spleen. A subset of patients with SM have an associated clonal hematologic neoplasm which is most commonly myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myelogenous leukemia and this entity is termed SM with associated hematological neoplasm (AHN). Bone marrow involvement is present in all patients regardless of the subtype of SM. The genetic hallmark of SM is a somatic gain-of-function point mutation within the KIT gene. Other molecular aberrations that have been reported include somatic mutations in TET2, SRSF2, ASXL1, CBL, RUNX1, and RAS and these are common in SM-AHN. The clinical presentation of SM can range from indolent to advanced depending on extent of mast cell burden and genetic profile. In the case of indolent SM, the goal of treatment is to control mediator release-related effects as well as to reduce mast cell burden. In the case of SM-AHN, therapy is primarily that of the AHN and allogeneic hematopoietic stem cell transplantation is the preferred therapy in suitable candidates.


Assuntos
Neoplasias Hematológicas , Mastocitose Sistêmica , Medula Óssea , Humanos , Mastócitos , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/terapia , Proteínas Proto-Oncogênicas c-kit
18.
Cells ; 10(10)2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34685733

RESUMO

Basophils and mast cells are among the principal inducers of Th2 responses and have a crucial role in allergic and anti-parasitic protective immunity. Basophils can function as antigen-presenting cells that bind antigens on their surface and boost humoral immune responses, inducing Th2 cell differentiation. Their depletion results in lower humoral memory activation and greater infection susceptibility. Basophils seem to have an active role upon immune response to SARS-CoV-2. In fact, a coordinate adaptive immune response to SARS-CoV-2 is magnified by basophils. It has been observed that basophil amount is lower during acute disease with respect to the recovery phase and that the grade of this depletion is an important determinant of the antibody response to the virus. Moreover, mast cells, present in a great quantity in the nasal epithelial and lung cells, participate in the first immune response to SARS-CoV-2. Their activation results in a hyperinflammatory syndrome through the release of inflammatory molecules, participating to the "cytokine storm" and, in a longer period, inducing pulmonary fibrosis. The literature data suggest that basophil counts may be a useful prognostic tool for COVID-19, since their reduction is associated with a worse prognosis. Mast cells, on the other hand, represent a possible therapeutic target for reducing the airway inflammation characteristic of the hyperacute phase of the disease.


Assuntos
Basófilos/citologia , COVID-19/imunologia , COVID-19/fisiopatologia , Mastócitos/citologia , Imunidade Adaptativa , Animais , COVID-19/sangue , Diferenciação Celular , Citocinas/metabolismo , Granulócitos/citologia , Humanos , Hipersensibilidade/metabolismo , Sistema Imunitário , Imunidade Humoral , Imunidade Inata , Inflamação , Macrófagos/citologia , Camundongos , SARS-CoV-2 , Células Th17/citologia , Células Th2/citologia
19.
Nutrients ; 13(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34684460

RESUMO

There is an ongoing need for new therapeutic modalities against SARS-CoV-2 infection. Mast cell histamine has been implicated in the pathophysiology of COVID-19 as a regulator of proinflammatory, fibrotic, and thrombogenic processes. Consequently, mast cell histamine and its receptors represent promising pharmacological targets. At the same time, nutritional modulation of immune system function has been proposed and is being investigated for the prevention of COVID-19 or as an adjunctive strategy combined with conventional therapy. Several studies indicate that several immunonutrients can regulate mast cell activity to reduce the de novo synthesis and/or release of histamine and other mediators that are considered to mediate, at least in part, the complex pathophysiology present in COVID-19. This review summarizes the effects on mast cell histamine of common immunonutrients that have been investigated for use in COVID-19.


Assuntos
COVID-19/imunologia , Histamina/imunologia , Sistema Imunitário/imunologia , Mastócitos/imunologia , Fenômenos Fisiológicos da Nutrição/imunologia , Transdução de Sinais/imunologia , Humanos , SARS-CoV-2
20.
J Cell Sci ; 134(9)2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34550354

RESUMO

Although RACK1 is known to act as a signaling hub in immune cells, its presence and role in mast cells (MCs) is undetermined. MC activation via antigen stimulation results in mediator release and is preceded by cytoskeleton reorganization and Ca2+ mobilization. In this study, we found that RACK1 was distributed throughout the MC cytoplasm both in vivo and in vitro. After RACK1 knockdown (KD), MCs were rounded, and the cortical F-actin was fragmented. Following antigen stimulation, in RACK1 KD MCs, there was a reduction in cortical F-actin, an increase in monomeric G-actin and a failure to organize F-actin. RACK1 KD also increased and accelerated degranulation. CD63+ secretory granules were localized in F-actin-free cortical regions in non-stimulated RACK1 KD MCs. Additionally, RACK1 KD increased antigen-stimulated Ca2+ mobilization, but attenuated antigen-stimulated depletion of ER Ca2+ stores and thapsigargin-induced Ca2+ entry. Following MC activation there was also an increase in interaction of RACK1 with Orai1 Ca2+-channels, ß-actin and the actin-binding proteins vinculin and MyoVa. These results show that RACK1 is a critical regulator of actin dynamics, affecting mediator secretion and Ca2+ signaling in MCs. This article has an associated First Person interview with the first author of the paper.


Assuntos
Actinas , Cálcio , Citoesqueleto de Actina , Actinas/genética , Humanos , Mastócitos , Proteínas de Neoplasias/genética , Receptores de Quinase C Ativada/genética , Tapsigargina
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