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1.
Nihon Shokakibyo Gakkai Zasshi ; 117(7): 626-634, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32655122

RESUMO

An 82-year-old male with a gallbladder mass was diagnosed with gallbladder carcinoma through various examinations. Cholecystectomy, gallbladder bed resection, and lymph node dissection were performed. The histological examination revealed a gallbladder adenosquamous carcinoma, and this tumor showed positive staining for granulocyte-colony stimulating factor (G-CSF). Recurrence of multiple liver metastases was detected on 25th day postoperatively. Unfortunately, the patient died on 97th day postoperatively. Here, we report a case of G-CSF-producing adenosquamous carcinoma of the gallbladder with rapid recurrence of liver metastases in the early postoperative period.


Assuntos
Carcinoma Adenoescamoso , Neoplasias da Vesícula Biliar , Neoplasias Hepáticas , Idoso de 80 Anos ou mais , Fator Estimulador de Colônias de Granulócitos , Granulócitos , Humanos , Masculino , Recidiva Local de Neoplasia
3.
Cardiovasc Ther ; 2020: 9783630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32405324

RESUMO

Introduction: Anticoagulants such as argatroban and heparins (low-molecular-weight and unfractionated) play an immense role in preventing thromboembolic complications in clinical practice. Nevertheless, they can also have a negative effect on the immune system. This study is aimed at investigating the influence of these substances on polymorphonuclear neutrophils (PMNs), whose nonspecific defense mechanisms can promote thrombogenesis. Methods: Blood samples from 30 healthy volunteers were investigated, whereby PMNs were isolated by density gradient centrifugation and incubated with 0.8 µg/mL of argatroban, 1.0 U/mL of low-molecular-weight heparin (LMWH), 1.0 U/mL of unfractionated heparin (UFH), or without drug (control). A collagen-cell mixture was prepared and filled into 3D µ-slide chemotaxis chambers (IBIDI® GmbH, Germany). Stimulation was initiated by using a chemokine gradient of n-formyl-methionine-leucyl-phenylalanine (fMLP), and microscopic observation was conducted for 4.5 hours. The cells' track length and track straightness, as well as the number of attracted granulocytes, level of ROS (reactive oxygen species) production, and NET (neutrophil extracellular traps) formation, were analyzed and categorized into migration distances and time periods. Results: All three anticoagulants led to significantly reduced PMN track lengths, with UFH having the biggest impact. The number of tracks observed in the UFH group were significantly reduced compared to the control group. Additionally, the UFH group demonstrated a significantly lower track straightness compared to the control. ROS production and NET formation were unaffected. Conclusion: Our data provide evidence that anticoagulants have an inhibitory effect on the extent of PMN migration and chemotactic migration efficiency, thus indicating their potential immune-modulatory and prothrombotic effects.


Assuntos
Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Quimiotaxia de Leucócito/efeitos dos fármacos , Enoxaparina/efeitos adversos , Granulócitos/efeitos dos fármacos , Ácidos Pipecólicos/efeitos adversos , Adulto , Armadilhas Extracelulares/metabolismo , Feminino , Granulócitos/imunologia , Granulócitos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Adulto Jovem
4.
Gan To Kagaku Ryoho ; 47(5): 851-853, 2020 May.
Artigo em Japonês | MEDLINE | ID: mdl-32408335

RESUMO

BACKGROUND: Pegfilgrastim, a long-acting granulocyte-colony-stimulating factor(G-CSF), has been used as prophylaxis for severe hematotoxicity induced by chemotherapy. We report a case of aortitis induced by pegfilgrastim administration during modified FOLFIRINOX(mFOLFIRINOX)chemotherapy for metastatic pancreatic cancer. CASE REPORT: A 65-year-old woman underwent a distal pancreatectomy for pancreatic tail cancer. Liver metastases appeared 2 years after the surgery. mFOLFIRINOX chemotherapy was started with prophylactic administration of pegfilgrastim. Eight days after the first administration and 6 days after administration of the 8th course, the patient developed a fever. The blood test results indicated severe inflammation. Computed tomography revealed a thickened aorta indicating aortitis. The symptoms rapidly improved with antibiotic therapy. We diagnosed aortitis induced by pegfilgrastim administration. CONCLUSION: Aortitis should be considered when a patient has unidentified inflammatory findings after receiving pegfilgrastim.


Assuntos
Aortite , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Neoplasias Pancreáticas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Aortite/induzido quimicamente , Feminino , Filgrastim , Granulócitos , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Polietilenoglicóis , Proteínas Recombinantes
5.
Ann Hematol ; 99(7): 1505-1514, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32390114

RESUMO

The International Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry (NCT01374360) was initiated to optimize patient management by collecting data regarding disease burden, progression, and clinical outcomes. Herein, we report updated baseline demographics, clinical characteristics, disease burden data, and observed trends regarding clone size in the largest cohort of Registry patients. Patients with available data as of July 2017 were stratified by glycosylphosphatidylinositol (GPI)-deficient granulocyte clone size (< 10%, ≥ 10%-< 50%, and ≥ 50%). All patients were untreated with eculizumab at baseline, defined as date of eculizumab initiation or date of Registry enrollment (if never treated with eculizumab). Outcomes assessed in the current analysis included proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVEs; including thrombotic events [TEs]), bone marrow failure (BMF), red blood cell (RBC) transfusions, and PNH-related symptoms. A total of 4439 patients were included, of whom 2701 (60.8%) had available GPI-deficient granulocyte clone size data. Among these, median clone size was 31.8% (1002 had < 10%; 526 had ≥ 10%-< 50%; 1173 had ≥ 50%). There were high proportions of patients with HDA (51.6%), history of MAVEs (18.8%), BMF (62.6%), RBC transfusion (61.3%), and impaired renal function (42.8%). All measures except RBC transfusion history significantly correlated with GPI-deficient granulocyte clone size. A large proportion of patients with GPI-deficient granulocyte clone size < 10% had hemolysis (9.7%), MAVEs (10.2%), HDA (9.1%), and/or PNH-related symptoms. Although larger GPI-deficient granulocyte clone sizes were associated with higher disease burden, a substantial proportion of patients with smaller clone sizes had history of MAVEs/TEs.


Assuntos
Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/epidemiologia , Adulto , Transtornos da Insuficiência da Medula Óssea/diagnóstico , Transtornos da Insuficiência da Medula Óssea/epidemiologia , Transtornos da Insuficiência da Medula Óssea/etiologia , Efeitos Psicossociais da Doença , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Granulócitos/patologia , Hemoglobinúria Paroxística/patologia , Hemoglobinúria Paroxística/terapia , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Sistema de Registros , Índice de Gravidade de Doença , Adulto Jovem
6.
J Med Virol ; 92(7): 856-862, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32281668

RESUMO

COVID-19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID-19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID-19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID-19, the lymphocytes in the severe COVID-19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C-reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = -.37; P < .01) was negatively correlated with the CT severity scores. The receiver-operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID-19 was 0.87 (95% CI 0.10-1.00) at 20.42 mg/L cut-off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID-19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Área Sob a Curva , Betacoronavirus/genética , Biomarcadores/sangue , Sedimentação Sanguínea , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Diagnóstico Precoce , Registros Eletrônicos de Saúde , Feminino , Granulócitos/patologia , Humanos , Influenza Humana/sangue , Influenza Humana/patologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Orthomyxoviridae/genética , Orthomyxoviridae/isolamento & purificação , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
7.
Cardiovasc Ther ; 2020: 7834173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292492

RESUMO

Extracorporeal hemadsorption may reduce inflammatory reaction in cardiopulmonary bypass (CPB) surgery. Glucocorticoids have been used during open-heart surgery for alleviation of systemic inflammation after CPB. We compared intraoperative hemadsorption and methylprednisolone, with usual care, during complex cardiac surgery on CPB, for inflammatory responses, hemodynamics, and perioperative course. Seventy-six patients with prolonged CPB were recruited and randomized, with 60 included in final analysis. Allocation was into three groups: Methylprednisolone (n = 20), Cytosorb (n = 20), and Control group (usual care, n = 20). Proinflammatory (TNF-α, IL-1ß, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines which complement C5a, CD64, and CD163 expression by immune cells were analyzed within the first five postoperative days, in addition to hemodynamic and clinical outcome parameters. Methylprednisolone group, compared to Cytosorb and Control had significantly lower levels of TNF-α (until the end of surgery, p < 0.001), IL-6 (until 48 h after surgery, p < 0.001), and IL-8 (until 24 h after surgery, p < 0.016). CD64 expression on monocytes was the highest in the Cytosorb group and lasted until the 5th postoperative day (p < 0.016). IL-10 concentration (until the end of surgery) and CD163 expression on monocytes (until 48 h after surgery) were the highest in the Methylprednisolone group (p < 0.016, for all measurements between three groups). No differences between groups in the cardiac index or clinical outcome parameters were found. Methylprednisolone more effectively ameliorates inflammatory responses after CPB surgery compared to hemadsorption and usual care. Hemadsorption compared with usual care causes higher prolonged expression of CD64 on monocytes but short lasting expression of CD163 on granulocytes. Hemadsorption with CytoSorb® was safe and well tolerated. This trial is registered with clinicaltrials.gov (NCT02666703).


Assuntos
Anti-Inflamatórios/administração & dosagem , Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Glucocorticoides/administração & dosagem , Hemadsorção , Inflamação/prevenção & controle , Metilprednisolona/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/efeitos adversos , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Citocinas/sangue , Feminino , Glucocorticoides/efeitos adversos , Granulócitos/efeitos dos fármacos , Granulócitos/imunologia , Granulócitos/metabolismo , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Mediadores da Inflamação/sangue , Masculino , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Estudos Prospectivos , Eslovênia , Fatores de Tempo , Resultado do Tratamento
9.
Am J Clin Pathol ; 153(4): 554-565, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32011681

RESUMO

OBJECTIVES: Previously we demonstrated that a decreased percentage of CD177-positive granulocytes detected by flow cytometry (FCM) was associated with myelodysplastic syndrome (MDS). Here we expand on those findings to more rigorously evaluate the utility of CD177 for the detection of MDS. METHODS: Two hundred patient samples (100 MDS and 100 controls) were evaluated for granulocyte expression of CD177 and 11 other flow cytometric parameters known to be associated with MDS. RESULTS: We show that CD177, as a single analyte, is highly correlated with MDS with a receiver operating characteristic area under curve value of 0.8. CD177 expression below 30% demonstrated a sensitivity of 51% and a specificity of 94% for detecting MDS with a positive predictive value of 89.5%. In multivariate analysis of 12 MDS-associated FCM metrics, CD177 and the Ogata parameters were significant indicators of MDS, and CD177 increased sensitivity of the Ogata score by 16% (63%-79%) for predicting MDS. Finally, diagnostic criteria incorporating these parameters with a 1% blast cutoff level and CD177 resulted in a sensitivity of 90% and specificity of 91% for detecting MDS. CONCLUSIONS: The findings indicate CD177 is a useful FCM marker for MDS.


Assuntos
Granulócitos/metabolismo , Isoantígenos/metabolismo , Síndromes Mielodisplásicas/diagnóstico , Receptores de Superfície Celular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI/metabolismo , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/metabolismo
10.
Exp Hematol ; 82: 33-42, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32045657

RESUMO

The erythroblastic island (EBI) is a multicellular structure forming an erythropoietic niche consisting of a central macrophage surrounded by a rosette of maturing erythroblasts. Since their discovery more than 60 years ago, simultaneous quantification and visualization of EBIs remain difficult. Although flow cytometry enables high-throughput quantification of cell aggregates co-expressing macrophage and erythroblast markers, it cannot visually confirm whether the aggregates are genuine EBIs. While immunofluorescence microscopy allows visualization of EBIs, its low throughput limits its use for quantification. In the current study we employed nine-channel imaging flow cytometry (IFC) to develop a method to directly visualize and quantify EBIs in the mouse bone marrow. We found that EBI central macrophages do express F4/80, VCAM-1, and CD169, but not CD11b or Ly6G, and that CD11b+Ly6G+F4/80- granulocytes are found associated at the periphery of 40%-60% EBIs. Furthermore, we show for the first time using IFC that in vivo treatment with the hematopoietic stem cell-mobilizing cytokine granulocyte colony-stimulating factor (G-CSF) reduced EBI frequency in the bone marrow by more than 100-fold. These results indicate that mobilizing doses of G-CSF cause a collapse of EBIs in the bone marrow.


Assuntos
Medula Óssea/metabolismo , Eritroblastos , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Granulócitos , Macrófagos , Animais , Antígenos de Diferenciação/biossíntese , Eritroblastos/citologia , Eritroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Granulócitos/citologia , Granulócitos/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos
11.
Arkh Patol ; 82(1): 30-37, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32096488

RESUMO

OBJECTIVE: To study the expression of IL-17A in the inflammatory infiltrating cells in the plaques as one of the key points in the pathological process in moderate to severe psoriasis. MATERIAL AND METHODS: The material obtained from 50 patients with moderate and severe psoriasis was examined by an indirect immunofluorescence assay to determine the composition of cell infiltrate and the type of IL-17A-producing cells in the foci of lesion. The markers of lymphocytes (CD3), dendritic cells (CD11c), neutrophilic granulocytes (Mpo), and mast cells (Trp) were used. The proliferative activity of basal keratinocytes (Ki-67), the expression of IL-17A, and the co-expression of IL-17A, Mpo, and Trp were also studied. RESULTS: A positive correlation was established between the count of neutrophilic granulocytes in the infiltrate, the expression of IL-17A, and the number of neutrophils expressing IL-17A with the duration of the disease and the severity of the patient's condition. CONCLUSION: Neutrophilic granulocytes and their expression of IL-17A play one of the key roles in the pathogenesis of psoriasis.


Assuntos
Psoríase , Granulócitos , Humanos , Interleucina-17 , Queratinócitos , Mastócitos
12.
Infect Immun ; 88(3)2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31907194

RESUMO

Yersinia pestis is the causative agent of bubonic, pneumonic, and septicemic plague. We demonstrate that Toll-like receptor 2-deficient (TLR2-/-) mice are resistant to septicemic infection by the KIM5 strain of Y. pestis but not to infection by the CO92 Δpgm strain. This resistance is dependent on TLR2, the route of infection, and the isoform of YopJ. Elevated bacterial burdens were found in the spleens of CO92 Δpgm-infected animals by 24 h postinfection and in the livers by 4 days. The YopJ isoform present contributed directly to cytotoxicity and inflammatory cytokine production of bone marrow-derived macrophages from TLR2-/- mice. Immune cell trafficking is altered in CO92 Δpgm infections, with an increased neutrophil infiltration to the spleen 5 days postinfection. Immune cell infiltration to the liver was greater and earlier in KIM5-infected TLR2-/- mice. The functionality of the immune cells was assessed by the ability to develop reactive oxygen and nitrogen species. Our data suggest an inhibition of granulocytes in forming these species in CO92 Δpgm-infected TLR2-/- mice. These findings suggest that resistance to KIM5 in TLR2-/- mice is dependent on early immune cell trafficking and functionality.


Assuntos
Peste/imunologia , Receptor 2 Toll-Like/deficiência , Yersinia pestis/patogenicidade , Animais , Carga Bacteriana , Proteínas de Bactérias/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Granulócitos/metabolismo , Fígado/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/imunologia , Neutrófilos/metabolismo , Peste/metabolismo , Peste/microbiologia , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Baço/imunologia , Baço/microbiologia , Receptor 2 Toll-Like/imunologia , Virulência/genética , Yersinia pestis/genética
13.
Einstein (Sao Paulo) ; 18: eAO4966, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31994605

RESUMO

OBJECTIVE: To validate multilineage score system correlating results of flow cytometry, cytogenetics, cytomorphology and histology from samples of patients with suspected myelodysplastic syndrome or cytopenia of unknown origin. METHODS: A retrospective study analyzing laboratory data of 49 patients with suspected myelodysplastic syndrome or cytopenia of unknown origin, carried out between May and September 2017. The inclusion criteria were availability of flow cytometry results, and at least one more method, such as morphology, histology or cytogenetics. Thirty-eight patients were classified as diagnosis of myelodysplastic syndromes, whereas 11 were classified as normal. Patients were evaluated based on score systems, Ogata score and flow cytometry multilineage score. RESULTS: Comparing the scores obtained in the Ogata score and the multilineage score, it was observed that in four cases the Ogata score was zero or 1 point, while the multilineage score was higher than 3 points. In addition, in 12 cases with Ogata score of 2, the multilineage score was greater than 3. CONCLUSION: The flow cytometry multilineage score system demonstrated to be more effective in dysplasia analysis, by assessing the erythroid, monocytic, granulocytic and precursor cell lineages, apart from the parameters evaluated by the Ogata score.


Assuntos
Citometria de Fluxo/normas , Síndromes Mielodisplásicas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Células da Medula Óssea/patologia , Criança , Pré-Escolar , Análise Citogenética/métodos , Análise Citogenética/normas , Células Eritroides/patologia , Feminino , Citometria de Fluxo/métodos , Granulócitos/patologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Padrões de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
14.
Am J Physiol Lung Cell Mol Physiol ; 318(2): L407-L418, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31644311

RESUMO

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.


Assuntos
Antibacterianos/efeitos adversos , Displasia Broncopulmonar/complicações , Lesão Pulmonar/induzido quimicamente , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/patologia , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Líquido da Lavagem Broncoalveolar , Displasia Broncopulmonar/fisiopatologia , Citocinas/metabolismo , Feminino , Granulócitos/metabolismo , Hiperóxia/complicações , Hiperóxia/fisiopatologia , Inflamassomos/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Pulmão/patologia , Lesão Pulmonar/microbiologia , Lesão Pulmonar/fisiopatologia , Camundongos Endogâmicos C57BL , Oxigênio/metabolismo , Fenótipo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/microbiologia , Análise de Sobrevida , Remodelação Vascular/efeitos dos fármacos
15.
Parasitol Res ; 119(1): 189-201, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31820168

RESUMO

For many years, the immune response of invertebrates was considered to lack any mechanism of memory. However, the study of their response has shown a kind of acquired immunity, which is not so well understood given the lack of knowledge of the invertebrate defense system. This event can be called "innate immune memory." Recent studies using Biomphalaria glabrata snails have reported this phenomenon, relating it to an increase in humoral products, but no focus was given to hemocyte response or to other species of snails. In this study, we focus on hemocyte dynamics and some humoral factors in the species B. glabrata and B. straminea, the most widespread species in Brazil, sensitized and non-sensitized to the Schistosoma mansoni worm. We report a change in the prevalent hemocyte type after sensitization, through an increase in the proportion of granulocytes, as well as a change in the total number of hemocytes caused by a second exposure to the parasite. We also showed that melanization is not a key factor in Biomphalaria snail defense and varies little after the second exposure event. The data reported in this article confirm the effect of immune priming on these snails and suggest that the increase of humoral products shown in the literature is accompanied by variation in hemocytes after sensitization.


Assuntos
Biomphalaria/imunologia , Biomphalaria/parasitologia , Hemócitos/imunologia , Memória Imunológica/imunologia , Schistosoma mansoni/imunologia , Animais , Brasil , Granulócitos/imunologia , Interações Hospedeiro-Parasita , Schistosoma mansoni/patogenicidade
17.
Ann Rheum Dis ; 79(2): 242-253, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31780527

RESUMO

OBJECTIVES: Haematopoietic stem and progenitor cells (HSPCs) are multipotent cells giving rise to both myeloid and lymphoid cell lineages. We reasoned that the aberrancies of immune cells in systemic lupus erythematosus (SLE) could be traced back to HSPCs. METHODS: A global gene expression map of bone marrow (BM)-derived HSPCs was completed by RNA sequencing followed by pathway and enrichment analysis. The cell cycle status and apoptosis status of HSPCs were assessed by flow cytometry, while DNA damage was assessed via immunofluorescence. RESULTS: Transcriptomic analysis of Lin-Sca-1+c-Kit+ haematopoietic progenitors from diseased lupus mice demonstrated a strong myeloid signature with expanded frequencies of common myeloid progenitors (CMPs)-but not of common lymphoid progenitors-reminiscent of a 'trained immunity' signature. CMP profiling revealed an intense transcriptome reprogramming with suppression of granulocytic regulators indicative of a differentiation arrest with downregulation trend of major regulators such as Cebpe, Cebpd and Csf3r, and disturbed myelopoiesis. Despite the differentiation arrest, frequencies of BM neutrophils were markedly increased in diseased mice, suggesting an alternative granulopoiesis pathway. In patients with SLE with severe disease, haematopoietic progenitor cells (CD34+) demonstrated enhanced proliferation, cell differentiation and transcriptional activation of cytokines and chemokines that drive differentiation towards myelopoiesis, thus mirroring the murine data. CONCLUSIONS: Aberrancies of immune cells in SLE can be traced back to the BM HSPCs. Priming of HSPCs and aberrant regulation of myelopoiesis may contribute to inflammation and risk of flare. TRIAL REGISTRATION NUMBER: 4948/19-07-2016.


Assuntos
Reprogramação Celular/imunologia , Células-Tronco Hematopoéticas/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Células Mieloides/imunologia , Transcriptoma/imunologia , Animais , Apoptose/imunologia , Proteína delta de Ligação ao Facilitador CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ciclo Celular/imunologia , Mapeamento Cromossômico , Dano ao DNA , Citometria de Fluxo , Imunofluorescência , Fator Estimulador de Colônias de Granulócitos/metabolismo , Granulócitos/imunologia , Linfócitos/imunologia , Camundongos
19.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165554, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513833

RESUMO

Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.


Assuntos
Fator Ativador de Células B/metabolismo , Linfócitos B/metabolismo , Interferon Tipo I/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Células Supressoras Mieloides/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/fisiologia , Animais , Citocinas/metabolismo , Progressão da Doença , Feminino , Granulócitos/metabolismo , Granulócitos/patologia , Humanos , Rim/metabolismo , Rim/patologia , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Células Supressoras Mieloides/patologia
20.
Blood Cells Mol Dis ; 80: 102372, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31710879

RESUMO

The marked pro-thrombotic tendency in PNH is likely to be at least partly due to the population of platelets derived from the abnormal stem cell clone. However, identification of GPI (-) platelets by flow cytometry can be technically difficult. Here we describe a technique that involves the addition of aspirin immediately after the separation of platelet rich plasma and the use of gel filtration to isolate platelets away from plasma proteins and other blood cells. In a study of 92 analyses of samples from 50 patients, we have demonstrated that the percentage of PNH platelets correlates well with the percentage of PNH granulocytes. We also provide data on several cases where there was an extreme discrepancy between the proportion of PNH granulocytes and red cells; in these cases, the demonstration of abnormal platelets suggests that the patient is likely to be at risk of thrombosis. We believe this test will be potentially useful in the evaluation of samples from such patients and may serve as a tool to investigate the causes of hypercoagulability in PNH.


Assuntos
Plaquetas/metabolismo , Hemoglobinúria Paroxística/sangue , Hemoglobinúria Paroxística/diagnóstico , Biomarcadores , Coagulação Sanguínea , Fracionamento Celular/métodos , Eritrócitos/metabolismo , Citometria de Fluxo/métodos , Granulócitos/metabolismo , Hemoglobinúria Paroxística/complicações , Humanos , Testes de Função Plaquetária , Curva ROC , Trombose/etiologia
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