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1.
Cir. pediátr ; 32(4): 185-189, oct. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-184107

RESUMO

Introducción. El índice neutrófilo-linfocito (INL) se ha postulado como marcador inflamatorio en distintas patologías abdominales como la apendicitis aguda (AA). Sin embargo, existen pocos estudios que determinen su asociación con el grado de severidad de la AA. Este es el primer estudio que analiza la utilidad del INL como factor predictor de peritonitis en la AA en niños. Material y métodos. Estudio observacional retrospectivo en pacientes intervenidos de AA durante los años 2017 y 2018. Se distribuyeron en dos grupos según el diagnóstico intraoperatorio (AA no complicada y AA con peritonitis). Se analizaron variables demográficas y analíticas. Se definió el INL como el cociente entre los valores absolutos de neutrófilos y linfocitos. Se determinó mediante curvas ROC la sensibilidad y especificidad para el diagnóstico de peritonitis de distintos parámetros analíticos. Resultados. Se incluyeron un total de 398 pacientes (AA no complicada n= 342 y AA con peritonitis n=56), con una edad media de 10,5±2,9 años. El INL presentó un área bajo la curva (AUC) de 0,78, significativamente superior a la determinación de leucocitos (AUC 0,71; p=0,002) y de neutrófilos (AUC 0,74; p=0,009). No se observaron diferencias al compararlo con la determinación de la proteína C reactiva (AUC 0,79; p=0,598). Se estimó el punto de corte de INL>8,75 con una sensibilidad y especificidad de 75,0 y 72,2% respectivamente. Conclusión. El INL se postula como una herramienta útil para predecir la presencia de peritonitis en AA, y podría considerarse una alternativa a otras determinaciones de mayor coste como la proteína C reactiva


Aim of the study. The neutrophilto-lymphocyte ratio (NLR) has been postulated as an inflammatory marker in several abdominal pathologies such as acute appendicitis (AA). However, there are few studies that determine its association with the degree of severity of AA. This is the first study that analyzes the usefulness of NLR as a predictor of peritonitis in children with AA. Methods. Retrospective observational study in patients treated of AA during the years 2017 and 2018. They were divided into two groups according to the intraoperative diagnosis (uncomplicated AA and AA with peritonitis). Demographic and analytical variables were analyzed. The NLR was defined as the quotient between the absolute values of neutrophils and lymphocytes. The sensitivity and specificity for the diagnosis of peritonitis of different analytical parameters were determined by ROC curves. Results. A total of 398 patients were included (uncomplicated AA n=342 and AA with peritonitis n=56), with a mean age of 10.5±2.9 years. The NLR had an area under the curve (AUC) of 0.78, significantly higher than the determination of leukocytes (AUC 0.71, p=0.002) and of neutrophils (AUC 0.74, p=0.009). No differences were observed when compared to the determination of C-reactive protein (AUC 0.79, p=0.598). A cut-off point of NLR>8.75 was estimated with a sensitivity and specificity of 75.0 and 72.2% respectively. Conclusions. The NLR is a useful tool to predict the presence of peritonitis in AA, and could be considered an alternative to other higher cost determinations such as C-reactive protein


Assuntos
Humanos , Masculino , Feminino , Criança , Apendicite/diagnóstico , Peritonite/diagnóstico , Linfócitos/fisiologia , Contagem de Leucócitos/métodos , Valor Preditivo dos Testes , Apendicite/sangue , Índice de Gravidade de Doença , Curva ROC , Estudos Retrospectivos
2.
DNA Cell Biol ; 38(11): 1402-1410, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31556705

RESUMO

Tumor antigen-induced lymphocyte transformation (LT) represents the antitumor cellular immunity, which might correlate with the cancer treatment outcome. Currently, there is no LT assay (LTA) routinely used in clinic. To establish a sensitive and convenient procedure for LTA, the same samples were used to simultaneously perform three assays: 5-ethynyl-2'-deoxyuridine (EdU) assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and carboxyfluorescein succinimidyl ester (CFSE) assay, and then the three results were compared. Several conditions were optimized: the LT harvest time, sources of lymphocytes (blood, lymph nodes, or spleen), the added amount of stimulatory tumor antigen and in vivo immunization priming time for LTA. The results of side-by-side comparison showed that (1) the 72 h for coculture of lymphocytes with tumor antigens was optimal time to harvest cells for LTA; (2) 50 µg/mL of tumor antigens was the optimal concentration for activation LT from three sources; (3) EdU incorporation was the sensitive and convenient assay for LTA as compared with MTT and CFSE assays; (4) the day 21-28 after in vivo priming immunization was the testing time for LTA; and (5) peripheral blood LT could be a good representative of whole body's lymphocyte reaction and practically easy cell source for LTA. This comparison of the three LTA in mouse model suggests that the EdU incorporation assay might be useful to evaluate the antitumor immunity stimulated by specific tumor vaccine or different anticancer therapies.


Assuntos
Antígenos de Neoplasias/imunologia , Bioensaio/métodos , Ativação Linfocitária/fisiologia , Linfócitos/fisiologia , Animais , Antineoplásicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Células Cultivadas , Técnicas de Cocultura , Monitoramento de Medicamentos/métodos , Feminino , Corantes Fluorescentes/análise , Corantes Fluorescentes/metabolismo , Humanos , Imunidade Celular/fisiologia , Imunoensaio/métodos , Camundongos , Camundongos Endogâmicos ICR
3.
Res Vet Sci ; 126: 150-154, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493682

RESUMO

Systemic inflammatory response syndrome (SIRS) is the manifestation of the systemic response to an infectious or non-infectious disease. We evaluated the association between erythrocyte parameters, including nucleated red blood cells (NRBCs) and leukocyte ratios (NLR, neutrophil-to-lymphocyte ratio; BLR, band neutrophil-to-lymphocyte ratio; BLNR, band neutrophil-to-neutrophil-to-lymphocyte ratio). A review of the medical records was conducted searching SIRS dogs among those admitted to our intensive care unit and a SIRS grading was obtained based on how many criteria were fulfilled. The Acute Patient Physiology and Laboratory Evaluation (APPLEfast) score was assessed in each dog. Survival rate was assessed 15 days after admission. Dogs with clinical and/or clinicopathological signs of hemolytic or hemorrhagic disorders were excluded. Dogs with ≥2 criteria of SIRS along with a documented underlying infectious cause were recorded as septic (32/90, 35%). A SIRS grading >2 (p = .001) and an APPLEfast score > 25 (p = .03) were associated with mortality. Twenty-two of SIRS dogs (24%) showed circulating NRBCs. The occurrence of circulating NRBCs was associated with the mortality in SIRS groups (p = .0025). The median NLR was 11.69 and NLR was lower in septic dogs compared to non-septic ones (p = .0272). APPLEfast, SIRS grading and circulating NRBCs may be considered as negative prognostic factors in canine SIRS. NLR could be a useful tool in dogs with SIRS, which was significantly lower in the septic group. Further prospective, large-scale studies investigating BLR and BNLR in canine SIRS are warranted.


Assuntos
Doenças do Cão/sangue , Linfócitos/fisiologia , Neutrófilos/fisiologia , Síndrome de Resposta Inflamatória Sistêmica/veterinária , Animais , Biomarcadores/sangue , Cães , Eritroblastos/fisiologia , Contagem de Eritrócitos , Eritrócitos , Feminino , Masculino , Estudos Prospectivos , Taxa de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/sangue
4.
Immunity ; 51(1): 185-197.e6, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31278058

RESUMO

Innate lymphoid cells (ILCs) promote tissue homeostasis and immune defense but also contribute to inflammatory diseases. ILCs exhibit phenotypic and functional plasticity in response to environmental stimuli, yet the transcriptional regulatory networks (TRNs) that control ILC function are largely unknown. Here, we integrate gene expression and chromatin accessibility data to infer regulatory interactions between transcription factors (TFs) and genes within intestinal type 1, 2, and 3 ILC subsets. We predicted the "core" TFs driving ILC identities, organized TFs into cooperative modules controlling distinct gene programs, and validated roles for c-MAF and BCL6 as regulators affecting type 1 and type 3 ILC lineages. The ILC network revealed alternative-lineage-gene repression, a mechanism that may contribute to reported plasticity between ILC subsets. By connecting TFs to genes, the TRNs suggest means to selectively regulate ILC effector functions, while our network approach is broadly applicable to identifying regulators in other in vivo cell populations.


Assuntos
Intestinos/fisiologia , Subpopulações de Linfócitos/fisiologia , Linfócitos/fisiologia , Animais , Diferenciação Celular , Linhagem da Célula , Plasticidade Celular , Montagem e Desmontagem da Cromatina , Repressão Epigenética , Redes Reguladoras de Genes , Imunidade Inata , Imunomodulação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-maf/genética , Transcriptoma
5.
Medicina (Kaunas) ; 55(7)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284487

RESUMO

Background and Objectives: Ischaemic stroke (IS) is the leading cause of death and disability worldwide. All stages of cerebral ischaemia, but especially acute phase, are associated with inflammatory response. Recent studies showed that neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) may be used to assess inflammation in IS. To test whether there is a relationship between these parameters and type of stroke treatment, we analysed NLR and LMR in IS patients treated with three different modalities. Materials and Methods: The study included 58 adults with acute IS. A total of 28 patients received intravenous thrombolysis. In another 10 patients, the thrombolytic therapy was followed by thrombectomy and 20 patients did not undergo causal treatment. Blood samples were obtained within 24 h of the stroke diagnosis to calculate NLR and LMR. Next, NLR and LMR of the study subgroups were compared. Results: Our study revealed that NLR was significantly higher in patients treated with thrombectomy following thrombolysis, compared to no causal treatment. Statistical analysis demonstrated that patients with high National Institutes of Health Stroke Scale (NIHSS) scores presented higher NLR than in those with low NIHSS scores. Additionally, patients with high-sensitivity C-reactive protein (hs-CRP) ≥ 3 mg/L presented with significantly higher NLR and significantly lower LMR than the group of patients with lower hs-CRP (<3 mg/L). Conclusions: The main finding of this pilot study was that NLR in IS patients treated using thrombectomy following thrombolysis was markedly higher than that in other treatment groups, which was associated with increased severity of the disease in these patients. Therefore, patients with higher NLR may be expected to have more severe stroke. The link between stroke severity and NLR deserves further study.


Assuntos
Inflamação/classificação , Linfócitos/fisiologia , Monócitos/fisiologia , Neutrófilos/fisiologia , Acidente Vascular Cerebral/sangue , Idoso , Contagem de Células Sanguíneas/métodos , Isquemia Encefálica/sangue , Isquemia Encefálica/classificação , Proteína C-Reativa/análise , Proteína C-Reativa/fisiologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Polônia , Estudos Prospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/classificação
6.
PLoS One ; 14(5): e0216232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150403

RESUMO

Analyzing data on 2,057 healthy subjects in the Dutch Lifelines database we explore the relationship between immune system responses, thyroid hormone functioning and people's mood that is expected to be moderated by social support. We focus (1) on the innate immune system cell count: monocytes, eosinophil granulocytes, basophilic granulocytes, neutrophil granulocytes; and thrombocytes; and (2) on the adaptive immune system cell count: lymphocytes (T, B and NK cells). Moods were measured on the positive (PA) and negative (NA) dimensions of the PANAS scale, divided in four groups based on their PA and NA median scores: hedonic, positive mood, negative mood and anhedonic. We focus further on (3) thyroid cells: T3 and T4; and (4) on social support. We found significant differences between mood groups and mean cell counts for basophilic granulocytes and thrombocytes but not for monocytes, eosinophil granulocytes and neutrophil granulocytes in the innate immune system. However, in the adaptive immune system we found mean lymphocyte cell counts to be different in all four mood groups. We also found that T3 and T4 levels differ significantly across all mood groups and work in very close association with lymphocytes to activate the adaptive immune system. These differences were most significant in the hedonic and anhedonic groups. The findings allow us to better understand mood groups, especially the hedonic and anhedonic groups, and open up new avenues for intervention.


Assuntos
Afeto , Fenômenos do Sistema Imunológico , Apoio Social , Hormônios Tireóideos/análise , Imunidade Adaptativa , Adolescente , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Imunidade Inata , Linfócitos/citologia , Linfócitos/imunologia , Linfócitos/fisiologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Filosofia , Adulto Jovem
7.
Int J Mol Sci ; 20(11)2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31212601

RESUMO

Programmed cell death-1 (PD-1) is a cell surface receptor that dampens adaptive immune responses. PD-1 is activated by the engagement of its ligands PDL-1 or PDL-2. This results in the inhibition of T cell proliferation, differentiation, cytokine secretion, and cytolytic function. Although a great deal is known about PD-1 mediated regulation of CD4+ and CD8+ T cells, its expression and function in innate lymphoid cells (ILCs) are yet to be fully deciphered. This review summarizes the role of PD-1 in (1) modulating ILC development, (2) ILC function, and (3) PD-1 signaling in ILC. Finally, we explore how PD-1 based immunotherapies may be beneficial in boosting ILC responses in cancer, infections, and other immune-related disorders.


Assuntos
Linfócitos/fisiologia , Receptor de Morte Celular Programada 1/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Imunoterapia , Linfócitos/metabolismo , Receptor de Morte Celular Programada 1/genética
8.
Pak J Pharm Sci ; 32(2): 601-606, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31081772

RESUMO

Experimental based evidence suggests that most of the medicinal plants possess a wide-ranging pharmacological and biological activity that may possibly protect tissues against O2-induced damages. The objectives of the current study are: first, to investigate the effects of Monotheca buxifolia and Bosea amherstiana on H2O2 induced DNA damage in human lymphocytes and second, to determine its effect on oxidative enzymes. Cells were treated at concentration of 100µg/mL with both plants. Alkaline Single Cell Gel Electrophoresis/comet assay were used for DNA damage analysis. Activities of antioxidant enzymes TBARS, SOD, CAT and POD were assayed on treatment with the extracts. Both plants species possess the protective role against H2O2-induced lymphocytes DNA. Dichloromethane (DCM) fraction of Monotheca buxifolia (H DNA 94.79±0.29%) and methanolic fraction of Bosea amherstiana (H DNA 93.63±2.23%) possess high protection Significantly decrease occur in status of antioxidant enzymes. This study indicates that both plants have potential in preventing oxidative damages/stress related diseases and would be suitably used as supplements in combination with conventional drug for the treatment of cancer like diseases.


Assuntos
Dano ao DNA/efeitos dos fármacos , Enzimas/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/fisiologia , Plantas Medicinais/química , Adulto , Amaranthaceae/química , Antioxidantes/metabolismo , Ensaio Cometa , Dano ao DNA/fisiologia , Feminino , Humanos , Peróxido de Hidrogênio/toxicidade , Masculino , Pessoa de Meia-Idade , Substâncias Protetoras/farmacologia , Sapotaceae/química
9.
Immunity ; 51(1): 104-118.e7, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31128961

RESUMO

Innate lymphoid cells (ILCs) play strategic roles in tissue homeostasis and immunity. ILCs arise from lymphoid progenitors undergoing lineage restriction and the development of specialized ILC subsets. We generated "5x polychromILC" transcription factor reporter mice to delineate ILC precursor states by revealing the multifaceted expression of key ILC-associated transcription factors (Id2, Bcl11b, Gata3, RORγt, and RORα) during ILC development in the bone marrow. This approach allowed previously unattained enrichment of rare progenitor subsets and revealed hitherto unappreciated ILC precursor heterogeneity. In vivo and in vitro assays identified precursors with potential to generate all ILC subsets and natural killer (NK) cells, and also permitted discrimination of elusive ILC3 bone marrow antecedents. Single-cell gene expression analysis identified a discrete ILC2-committed population and delineated transition states between early progenitors and a highly heterogeneous ILC1, ILC3, and NK precursor cell cluster. This diversity might facilitate greater lineage potential upon progenitor recruitment to peripheral tissues.


Assuntos
Medula Óssea/imunologia , Subpopulações de Linfócitos/fisiologia , Linfócitos/fisiologia , Células Progenitoras Linfoides/fisiologia , Fatores de Transcrição/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Linhagem da Célula , Regulação da Expressão Gênica no Desenvolvimento , Genes Reporter , Imunidade Inata , Células Matadoras Naturais/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Análise de Célula Única , Fatores de Transcrição/genética
10.
Rev Neurol (Paris) ; 175(6): 396-402, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31027862

RESUMO

OBJECTIVE: This study was designed to investigate the impact of astrocyte and lymphocyte (LC) interactions in the blood-brain barrier (BBB) on the pathogenesis of multiple sclerosis (MS). METHODS: Primary rat brain microvascular endothelial cells (rBMECs) and astrocytes isolated from Sprague-Dawley rats were used to establish in vitro BBB models. Transendothelial electrical resistance (TEER) and permeability were compared between rBMEC monocultures and rBMEC/astrocyte co-cultures to evaluate the validity of each as a BBB cell model. rBMEC/LC co-cultures and rBMEC/astrocyte/LC tri-cultures were established to evaluate inflammatory responses in MS by measuring the gene expression levels of nerve growth factor (NGF), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), interleukin 17 (IL-17), interferon γ (IFN-γ), and forkhead box P3 (Foxp3). RESULTS: The rBMEC/astrocyte co-cultures exhibited higher TEER values and lower lymphocyte permeabilities than those of rBMEC monocultures. Compared to the rBMEC mono-cultures, the rBMEC/astrocyte/LC tri-cultures showed significantly decreased NGF, IL-17, and IFN-γ and increased MMP-2 and Foxp3 expression. Furthermore, the tri-cultures exhibited decreased NGF, IL-17, and IFN-γ expression compared to the rBMEC/astrocyte co-cultures, and increased MMP-2 expression compared to that shown by the rBMEC/LC co-cultures. MMP-9 expression did not vary significantly between the four established BBB cell models. CONCLUSION: These results suggest that the synergistic effect between astrocytes and LCs may increase the expression of MMP-2 and decrease that of IL-17 and IFN-γ at the BBB. Furthermore, the use of rBMEC/astrocytes/LC tri-cultures enabled us to test the synergistic effect between astrocytes and LCs and their roles in MS pathogenesis.


Assuntos
Astrócitos/fisiologia , Barreira Hematoencefálica/patologia , Comunicação Celular/fisiologia , Linfócitos/fisiologia , Esclerose Múltipla/patologia , Animais , Astrócitos/patologia , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/fisiologia , Células Cultivadas , Técnicas de Cocultura , Impedância Elétrica , Células Endoteliais/fisiologia , Linfócitos/patologia , Esclerose Múltipla/imunologia , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley
11.
Biomed Pharmacother ; 114: 108833, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30978525

RESUMO

Age-related changes such as increased oxidative stress and DNA damage are important risk factors for Alzheimer's disease (AD). This study aimed to clarify the role of POLD1, the catalytic subunit of DNA polymerase δ, in neurodegeneration symptoms of AD. POLD1 expression levels were evaluated in patients with different neurodegenerative diseases by ELISA, RT-PCR and Western blot analysis. The impairment of cognitive ability in AD patients and senescence-accelerated mouse prone 8 (SAMP8) mice were evaluated by MMSE/MoCA score and Morris water maze (MWM) test. We found that serum concentration and expression levels of POLD1 in lymphocytes were reduced in AD patients. The cognitive impairment in AD patients and SAMP8 mice was associated with reduced POLD1 expression. In addition, POLD1 knockdown led to premature senescence and increased DNA damage in primary neuronal cells of SAMP8 mice. In conclusion, this is the first study suggesting that the deficiency of POLD1 may aggravate AD progression, and POLD1 is a potential diagnostic marker and therapeutic target for AD.


Assuntos
Doença de Alzheimer/genética , Transtornos Cognitivos/genética , Cognição/fisiologia , Disfunção Cognitiva/genética , DNA Polimerase III/deficiência , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Animais , Modelos Animais de Doenças , Feminino , Humanos , Linfócitos/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Pessoa de Meia-Idade , Estresse Oxidativo/genética
12.
J Therm Biol ; 81: 73-81, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30975426

RESUMO

This study aims to investigate the thermoprotective properties of Opuntia ficus-indica f. inermis. Extracts were prepared from cladodes (CE) and mesocarps (ME), then subjected to a spectrophotometric and LC-MS analyses. Lymphocytes were isolated from peripheral blood of non-stressed sheep, supplemented with CE, ME, betanin or α-tocopherol, and subjected to two thermal treatments: 40 and 41 °C, for 6 h. Viable lymphocytes and H2O2 production were evaluated. The antioxidant activity of ME was 3.43 folds higher than CE. The LC-MS analysis of CE and ME allowed identifying 11 phenolic acids, 2 flavanones, 6 flavones, 3 flavonols and 1 betanin type betacyanin. Lymphocytes mortality increased linearly as function of the severity and the duration of heat stress. This mortality was correlated with H2O2 production. At 41 °C, only ME allowed maintaining lymphocytes viability. Moreover, ME was more efficient than CE in reducing H2O2 production. This thermoprotection was ensured by betaxanthin and betacyanin pigments. Interestingly, betanin was more efficient than α-tocopherol in preventing hyperthermia-induced lymphocytes' mortality. We report here for the first time the thermoprotective properties of cladodes and mesocarps of Opuntia ficus-indica f. inermis. Betanin was able to maintain lymphocyte viability through reducing H2O2 production, and therefore the oxidative-induced heat stress.


Assuntos
Antioxidantes/administração & dosagem , Resposta ao Choque Térmico , Linfócitos/fisiologia , Opuntia/química , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Antioxidantes/química , Betacianinas/administração & dosagem , Betacianinas/isolamento & purificação , Betacianinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Suplementos Nutricionais , Peróxido de Hidrogênio/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ovinos , alfa-Tocoferol/administração & dosagem , alfa-Tocoferol/isolamento & purificação
13.
Presse Med ; 48(3 Pt 1): 255-261, 2019 Mar.
Artigo em Francês | MEDLINE | ID: mdl-30857807

RESUMO

Asthma is often associated with a Th2-type immune response with well-known cellular and molecular actors such as eosinophils, Th2 lymphocytes and associated cytokines such as interleukin-5 or IL-4. Nevertheless, some of the asthmatic patients show clinical manifestations and characteristics that do not correspond to the current pattern of the pathophysiology of asthma. Thus, recently new cellular and molecular actors in the development of asthma have been demonstrated in animal models and in humans. Among these are components of the innate immune system such as type 2 innate lymphoid cells or adaptive immune system such as Th9 lymphocytes. At the cellular level, the role of small G proteins in asthma is also highlighted as well as the role of major cytokines like IL-17 or those derived from the epithelium. A better knowledge of the physiopathology of asthma and the taking into account of these new actors allows the identification of new therapeutic targets for different endotypes of patients.


Assuntos
Asma/imunologia , Asma/fisiopatologia , Humanos , Linfócitos/fisiologia
14.
J Immunol Res ; 2019: 6705949, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30886872

RESUMO

Monitoring immune responses to solid cancers may be a better prognostic tool than conventional staging criteria, and it can also serve as an important criterion for the selection of individualized therapy. Multiparametric phenotyping by mass cytometry extended possibilities for immunoprofiling. However, careful optimization of each step of such method is necessary for obtaining reliable results. Also, with respect to procedure length and costs, sample preparation, staining, and storage should be optimized. Here, we designed a panel of 31 antibodies which allows for identification of several subpopulations of lymphoid and myeloid cells in a solid tumor and peripheral blood simultaneously. For sample preparation, disaggregation of tumor tissue with two different collagenases combined with DNase I was compared, and removal of dead or tumor cells by magnetic separation was evaluated. Two possible procedures of barcoding for single-tube staining of several samples were examined. While the palladium-based barcoding affected the stability of several antigens, the staining with two differently labeled CD45 antibodies was suitable for cells isolated from a patient's blood and tumor. The storage of samples in the intercalation solution for up to two weeks did not influence results of the analysis, which allowed the measurement of samples collected within this interval on the same day. This procedure optimized on samples from patients with head and neck squamous cell carcinoma enabled identification of various immune cells including rare subpopulations.


Assuntos
Imunofenotipagem/métodos , Linfócitos/fisiologia , Células Mieloides/fisiologia , Neoplasias/imunologia , Anticorpos Monoclonais/metabolismo , Separação Celular , Colagenases/metabolismo , Código de Barras de DNA Taxonômico , Desoxirribonuclease I/metabolismo , Citometria de Fluxo , Humanos , Antígenos Comuns de Leucócito/imunologia , Neoplasias/diagnóstico , Paládio/metabolismo , Análise de Célula Única
15.
Autoimmun Rev ; 18(5): 549-555, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30844559

RESUMO

Interleukin (IL)-13 is a cytokine playing a pivotal role in T helper (Th)2 immune response supposed to be implicated in some intestinal disorders. IL-13 is produced by Th2 cells, natural killer T cell, innate lymphoid cells and innate immune cells, which contribute to trigger and maintain a chronic idiopathic intestinal inflammation. In murine models IL-13 exerts pleiotropic functions, playing either pathogenic or protective roles according to the different experimental conditions. As regards celiac disease, IL-13 is considered to be involved mostly in the refractory phase rather than at uncomplicated stage. Discrepancies have been observed in the role of IL-13 upon the inflammation and fibrosis in ulcerative colitis (UC) and in Crohn's disease, respectively. Failure of the anti-IL-13 monoclonal antibodies tralokinumab and anrukinzumab in UC patients in clinical trials support the absence of a role for IL-13 in UC. This review deals with IL-13 in several experimental colitis models -such as oxazolone-, trinitrobenzene sulfonic acid- or dextran sodium sulphate-induced colitis- and chronic intestinal inflammatory disorders -including celiac disease, UC and Crohn's disease-, and it also highlights the attempts to modulate IL-13 as therapeutic tool.


Assuntos
Doenças Inflamatórias Intestinais/etiologia , Interleucina-13/fisiologia , Animais , Doença Crônica , Humanos , Imunidade Inata/fisiologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/terapia , Mucosa Intestinal/imunologia , Linfócitos/fisiologia , Camundongos , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(2): 252-256, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30827322

RESUMO

OBJECTIVE: Intestinal barrier act as the crucial defender against pathogen invasion, and is indispensable in maintaining tissue homeostasis both locally and systemically. Severe disease can lead to impaired intestinal barrier. In addition to cause a variety of gastrointestinal diseases, intestinal barrier damage can also worsen the disease progression in critically ill patients. Innate lymphoid cells (ILCs) is a group of newly defined innate immune cells which have some characteristics as adaptive immune cells. Group 3 innate lymphoid cells (ILC3), which mainly reside at gut associate mucosal tissue, have been reported to play a critical role in maintaining intestinal barrier function. After a brief introduction about its origination and classification, we will focus on function of ILC3 physiologically and pathologically, and provide a new theoretical basis for maintaining intestinal barrier function under pathological conditions in this review.


Assuntos
Imunidade Inata , Intestinos/citologia , Linfócitos/fisiologia , Homeostase , Humanos
17.
Ginekol Pol ; 90(2): 109-113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30860279

RESUMO

Fetal survival and development is supported by the maternal immune system. Questions regarding those mechanisms have risen from development of transplantation medicine and observation of graft rejection. Initial theories of anatomic division, fetal immune immaturity and maternal immune system inertia were found incorrect. Rejection of fetal "semi-allograft" by maternal immune system could result in pregnancy loss. Two pregnancy losses of any etiology are considered recurrent and effort should be made to name the probable cause. Immune causes of pregnancy loss are probably multifactorial, thus difficult to research and implement findings in clinical practice. Although a full understating of pregnancy loss is not established, new therapies are being developed. This review summarizes the role of lymphocytes in pregnancy develop- ment, presents data from studies on recurrent pregnancy loss patients, evidence of new therapies and ESHRE guidelines regarding immunologic investigations.


Assuntos
Aborto Habitual , Desenvolvimento Fetal , Linfócitos , Aborto Habitual/imunologia , Aborto Habitual/fisiopatologia , Aborto Habitual/terapia , Feminino , Desenvolvimento Fetal/imunologia , Desenvolvimento Fetal/fisiologia , Humanos , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/fisiologia , Gravidez , Linfócitos T Reguladores/imunologia , Células Th17/imunologia
18.
Biotech Histochem ; 94(5): 352-359, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30864862

RESUMO

Acrylamide is an important industrial chemical; it also is formed in starch-rich foodstuffs during baking, frying and roasting. Most acrylamide exposure occurs by ingestion of processed foods. We investigated possible immunotoxic effects of extended administration of low doses of acrylamide in rats. To do this, we measured alpha-naphthyl acetate esterase (ANAE) and acid phosphatase (ACP-ase) activities in peripheral blood lymphocytes. Male and female weanling Wistar rats were administered 2 or 5 mg acrylamide/kg/day in drinking water for 90 days. Peripheral blood was sampled at the end of the administration period. We found ANAE staining in eosinophils and T-lymphocytes, but not in monocytes, platelets, B-lymphocytes and neutrophils. ACP-ase was found in B-lymphocytes. We found a significant reduction of the ratio of ANAE:ACP-ase in lymphocytes of the experimental animals compared to controls. We found no statistically significant differences between the doses or sexes. We found that acrylamide ingested in processed foods might affect the immune system adversely by decreasing the population of mature T- and B-lymphocytes.


Assuntos
Fosfatase Ácida/metabolismo , Acrilamida/administração & dosagem , Acrilamida/toxicidade , Linfócitos/fisiologia , Naftol AS D Esterase/metabolismo , Fosfatase Ácida/sangue , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Histocitoquímica , Masculino , Naftol AS D Esterase/sangue , Ratos , Ratos Wistar , Fatores Sexuais
19.
Eur J Clin Invest ; 49(5): e13085, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30740673

RESUMO

BACKGROUND: Atherosclerosis represents a cardiovascular risk. Chronic inflammation is a key factor for atherogenic progression. Neutrophil-to-lymphocyte ratio (NLR) has been proposed as a novel biomarker for cardiovascular risks. We aimed to explore whether NLR was related to surrogate pro-atherogenic promoters driving atherogenic progression, as measured by carotid intima-media thickness (CIMT). STUDY DESIGN: Thirty-one patients with obesity candidates for bariatric surgery were recruited from Centro Médico Nacional "20 de Noviembre", ISSSTE, Mexico City. The results are part of the "CROP" study (NCT03561987). NLR was calculated from routine complete blood count, and its relation with plasma pro-inflammatory mediators (hsCRP, TNF-α and IL-1ß), adipokines (adiponectin and leptin), adiposity markers (visceral adipose tissue [VAT] determined from CT scan image and VAT individual adipocyte area at histological sample) and CIMT were determined. RESULTS: Neutrophil-to-lymphocyte ratio correlated with hsCRP (Spearman's r = 0.70 [95% CI 0.46 to 0.85], P < 0.01), TNF-α (r = 0.69 [0.44 to 0.84], P < 0.0001) and adiponectin (r = -0.69 [-0.84 to -0.45], P < 0.03), as well as with VAT individual adipocyte area (r = 0.64 [0.37 to 0.81], P < 0.0001) and with VAT area (r = 0.43; [0.07 to 0.68], P < 0.01). Leptin and adiponectin showed further independent association with higher NLR (multivariate regression analysis OR 7.9 [95% CI 1.1 to 56.2] P = 0.03 and 0.1 [0.01 to 1.0] P = 0.05, respectively). Moreover, NLR distribution significantly varied between subgroups divided according to progressive CIMT (P = 0.05); whereas adiponectin and VAT adipocyte area associated with CIMT > 0.9 mm (univariate analysis OR 0.1 [0.01 to 1.0] P = 0.05 and 13.1 [1.4 to 126.3] P = 0.03, respectively). CONCLUSION: Neutrophil-to-lymphocyte ratio was related to pro-inflammatory, adiposity biomarkers and progressive subclinical atherogenesis.


Assuntos
Adipocinas/metabolismo , Aterosclerose/etiologia , Citocinas/metabolismo , Adiposidade/fisiologia , Adulto , Aterosclerose/sangue , Aterosclerose/patologia , Biomarcadores/metabolismo , Espessura Intima-Media Carotídea , Progressão da Doença , Feminino , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Linfócitos/fisiologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/fisiologia , Obesidade/sangue , Obesidade/patologia , Estudos Prospectivos
20.
Mediators Inflamm ; 2019: 1978094, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804706

RESUMO

Innate lymphoid cells (ILCs) are a novel family of innate immune cells that act as key coordinators of intestinal mucosal surface immune defense and are essential for maintaining intestinal homeostasis and barrier integrity by responding to locally produced effector cytokines or direct recognition of exogenous or endogenous danger patterns. ILCs are also involved in the pathogenesis of inflammatory bowel disease (IBD). Many studies have demonstrated the occurrence of crosstalk between ILCs and intestinal microbiota, and ILCs have recently been shown to be connected to the enteric nervous system (ENS). Thus, ILCs may act as a key link between the nervous system and microbiota in intestinal networks. In this review, we briefly summarize the role of the ILCs in the intestinal tract (particularly in the context of IBD) and discuss the relationship between ILCs and the microbiota/ENS.


Assuntos
Imunidade Inata/imunologia , Linfócitos/imunologia , Microbiota/imunologia , Animais , Humanos , Imunidade Inata/fisiologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/fisiopatologia , Intestinos/imunologia , Intestinos/fisiopatologia , Linfócitos/fisiologia , Microbiota/fisiologia
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