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1.
PLoS One ; 15(12): e0243759, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33326471

RESUMO

Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest. [NCT01694160 (2012/107D)]; [www.clinicaltrials.gov].


Assuntos
Ergocalciferóis/farmacologia , Transplante de Rim/efeitos adversos , Biomarcadores/sangue , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/sangue , Inflamação/etiologia , Inflamação/imunologia , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade
2.
Rev Med Suisse ; 16(705): 1613-1617, 2020 Sep 09.
Artigo em Francês | MEDLINE | ID: mdl-32914592

RESUMO

Differential blood count is an excellent complementary test to complete blood count, which allows analysis of the white cell differentiation and their morphologic particularity. As the tendency currently leads to targeted laboratory analysis, differential blood count provides a diagnostic and prognostic value in many clinical situations, notably in patients with an infection. Based on clinical cases, this article reviews the different white blood cell lines to provide key points for interpretation of qualitative and quantitative anomalies encountered in the daily hospital practice.


Assuntos
Contagem de Leucócitos , Leucócitos/citologia , Técnicas de Laboratório Clínico , Hospitais , Humanos , Prognóstico
3.
PLoS One ; 15(9): e0238750, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886728

RESUMO

PURPOSE: The purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal. METHODS: Six-week-old male C57BL/6 mice were fed a high fat diet (HFD) or a normal diet (ND) for 5-15 weeks. Diet reversal (DiR) mice were fed a HFD for 5 weeks, followed by a ND for 5 or 10 weeks. Corneal sensitivity was determined using aesthesiometry. Corneal cytokine expression was analyzed using a 32-plex Luminex assay. Excised corneas were prepared for immunofluorescence microscopy to evaluate diet-induced changes and wound healing. For wounding studies, mice were fed a HFD or a ND for 10 days prior to receiving a central 2mm corneal abrasion. RESULTS: After 10 days of HFD consumption, corneal sensitivity declined. By 10 weeks, expression of corneal inflammatory mediators increased and nerve density declined. While diet reversal restored nerve density and sensitivity, the corneas remained in a heightened inflammatory state. After 10 days on the HFD, corneal circadian rhythms (limbal neutrophil accumulation, epithelial cell division and Rev-erbα expression) were blunted. Similarly, leukocyte recruitment after wounding was dysregulated and accompanied by delays in wound closure and nerve recovery. CONCLUSION: In the mouse, obesogenic diet consumption results in corneal dysfunction that precedes the onset of sustained hyperglycemia. Diet reversal only partially ameliorated this dysfunction, suggesting a HFD diet may have a lasting negative impact on corneal health that is resistant to dietary therapeutic intervention.


Assuntos
Córnea/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Hiperglicemia/fisiopatologia , Obesidade/induzido quimicamente , Obesidade/complicações , Animais , Composição Corporal/efeitos dos fármacos , Córnea/efeitos dos fármacos , Modelos Animais de Doenças , Homeostase/efeitos dos fármacos , Hiperglicemia/complicações , Leucócitos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo , Cicatrização/efeitos dos fármacos
4.
Toxicol Lett ; 333: 140-149, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32755622

RESUMO

Chrysotile is the only type of asbestos still widely exploited, and all kinds of asbestos including chrysotile was classified as a group I carcinogen by the IARC. There is a wealth of evidence that chrysotile can cause a range of cancers, including cancer of the lung, larynx, ovary, and mesothelioma. As the second largest chrysotile producer, China is at great risk of occupational exposure. Moreover, our previous experiment and some other studies have shown that the toxicity of mineral fibre from various mining areas may be different. To explore the oncogenic potential of chrysotile from different mining areas of China, Wistar rats were administered 0.5 mL chrysotile asbestos suspension of 2.0 mg/mL (from Akesai, Gansu; Mangnai, Qinghai; XinKang, Sichuan; and Shannan, Shaanxi) dissolved in saline by intratracheal instillation once-monthly and were sacrificed at 1 mo, 6 mo, and 12 mo. Our results found that chrysotile caused lung inflammation and lung tissue damage. Moreover, prolonged exposure of chrysotile can induce inactivation of the tumor suppressor gene P53 and P16 and activation of the protooncogene C-JUN and C-FOS both in the messenger RNA and protein level. In addition, chrysotile from Shannan and XinKang has a stronger effect which may link to cancer than that from Akesai and Mangnai.


Assuntos
Asbestos Serpentinas/toxicidade , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Poluentes Ambientais/toxicidade , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Pulmão/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Asbestos Serpentinas/química , Líquido da Lavagem Broncoalveolar/citologia , China , Inibidor p16 de Quinase Dependente de Ciclina/genética , Citocinas/metabolismo , Poluentes Ambientais/química , Expressão Gênica/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Contagem de Leucócitos , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Fibras Minerais/toxicidade , Proteínas Proto-Oncogênicas c-fos/genética , Ratos Wistar , Proteína Supressora de Tumor p53/genética
5.
PLoS One ; 15(8): e0237992, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845912

RESUMO

The leukocyte profile has the potential to be a reliable method to measure health conditions and stress in wild animals, but limitations occur because current knowledge on reference intervals is largely incomplete, especially because data come from studies on captive animals involving few individuals from single populations. Here we propose a general framework for achieving reliable leukocyte reference intervals, encompassing a set of internal and external factors, potentially affecting the leukogram. To do so, we present a systematic survey of the hematology of the common wall lizard, Podarcis muralis, involving 794 lizards from 54 populations over the whole geographic range of the species in Italy. Reference intervals for white blood cell (WBC) and leukocyte differential count were obtained by using linear mixed models in a Bayesian framework. The application of the procedure clearly showed that both internal (sex and size) and external (latitude and season) factors are a source of variation of leukocyte profile. Furthermore, the leukogram of common wall lizard has a strong variability among populations, which accounts for more than 50% of the whole variation. Consequently, some common assumptions used in studies on captive individuals are no longer supported in wild populations, namely, i) any group of individuals is a representative sample, ii) any population is representative of all others, iii) geographic clines do not occur over the species range, and iv) seasonal variation has limited effects. We encourage researchers aimed at the definition of leukocyte reference intervals for wild populations of reptiles to involve a large number of populations over a wide geographic range in ad hoc statistical models to disentangle local and geographic effects on leukocyte profile variation.


Assuntos
Leucócitos/citologia , Animais , Animais Selvagens , Teorema de Bayes , Tamanho Corporal , Feminino , Contagem de Leucócitos , Modelos Lineares , Lagartos , Masculino , Estações do Ano
6.
PLoS One ; 15(8): e0238006, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857814

RESUMO

This study aimed to evaluate the effects of two prebiotics in different concentrations on nutrient digestibility, fermentative products and immunological variables in adult dogs. Twenty-four adult dogs were randomly divided into six blocks according to their metabolic body weights (BW0.75); within these groups, dogs were randomized to four treatments: control without prebiotics (CO); inclusion of 0.5% prebiotic blend Yes-Golf (B1); inclusion of 1.0% galactooligosaccharide (GOS); and inclusion of 1.0% prebiotic blend Yes-Golf (B2). The experiment lasted 30 days, with 20 days adaptation and 10 days stool and blood collection. Results were analyzed for normality and means were separated by ANOVA and adjusted by the Tukey test at the significance level of 5.0%. Prebiotic supplementation had no effect on apparent digestibility coefficients (ADC), total stool production and fecal scores (p > 0.05). Prebiotics evaluated also did not alter fecal pH, nor the concentrations of ammonia, lactic acid, short chain fatty acids (SCFA) and most fecal branched chain fatty acids (BCFA) (p > 0.05). The addition of GOS decreased the concentration of iso-valeric acid (p = 0.0423). Regarding immunological variables, concentrations of fecal IgA were not influenced by the treatments. Treatments GOS and B2 increased the total number of polymorphonuclear cells, as well as the oxidative burst in relation to treatments B1 and CO (p < 0.0001). Treatment B2 improved the rate of S. aureus phagocytosis in relation to CO (p = 0.0111), and both the GOS and B2 treatments had a better index for E. coli phagocytosis than the CO treatment (p = 0.0067). In conclusion, there was indication that both prebiotics GOS and B2 at 1.0% inclusion improved the immunity of healthy dogs.


Assuntos
Colo/efeitos dos fármacos , Oligossacarídeos/farmacologia , Prebióticos , Animais , Colo/imunologia , Colo/microbiologia , Dieta/veterinária , Cães , Ácidos Graxos Voláteis/análise , Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Fagocitose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/fisiologia
7.
Proc Natl Acad Sci U S A ; 117(29): 17041-17048, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32632001

RESUMO

A central task in developmental biology is to learn the sequence of fate decisions that leads to each mature cell type in a tissue or organism. Recently, clonal labeling of cells using DNA barcodes has emerged as a powerful approach for identifying cells that share a common ancestry of fate decisions. Here we explore the idea that stochasticity of cell fate choice during tissue development could be harnessed to read out lineage relationships after a single step of clonal barcoding. By considering a generalized multitype branching process, we determine the conditions under which the final distribution of barcodes over observed cell types encodes their bona fide lineage relationships. We then propose a method for inferring the order of fate decisions. Our theory predicts a set of symmetries of barcode covariance that serves as a consistency check for the validity of the method. We show that broken symmetries may be used to detect multiple paths of differentiation to the same cell types. We provide computational tools for general use. When applied to barcoding data in hematopoiesis, these tools reconstruct the classical hematopoietic hierarchy and detect couplings between monocytes and dendritic cells and between erythrocytes and basophils that suggest multiple pathways of differentiation for these lineages.


Assuntos
Linhagem da Célula , Código de Barras de DNA Taxonômico/métodos , Animais , Linhagem da Célula/genética , Linhagem da Célula/fisiologia , Árvores de Decisões , Células Dendríticas/citologia , Eritrócitos/citologia , Hematopoese/genética , Hematopoese/fisiologia , Leucócitos/citologia , Modelos Biológicos , Biologia de Sistemas
8.
PLoS One ; 15(6): e0233913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574170

RESUMO

BACKGROUND: Leukocyte alterations are a common hematological alteration among malaria patients. OBJECTIVES: This systematic review and meta-analysis aimed to provide data and evidence comparing alterations in total leukocyte counts in malaria patients compared to febrile/healthy subjects at baseline before treatment. A systematic review was conducted by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analyses. DATA SOURCES: Web of Science (ISI), Scopus, and Medline. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: All published articles reporting a total leukocyte count of patients infected with malaria, non-malaria (febrile or healthy group) at baseline before treatment before August 27, 2019, were retrieved, and data were extracted by two main reviewers independently. STUDY APPRAISAL AND SYNTHESIS METHODS: We used a forest plot, heterogeneity test (Cochran's Q), and the degree of heterogeneity (I2) to test whether the included studies were heterogeneous. The quality of the included studies was determined by a quality assessment guide based on the quality assessment tool developed by the Newcastle-Ottawa Scale (NOS). Cochran's Q (Chi-square) and Moran's I2 were used to evaluate heterogeneity. Meta-regression using STATA software was conducted to find the source of heterogeneity. A funnel plot with Egger's test was used to examine the significance of publication bias among the included studies. The mean differences were estimated using a random-effects model. RESULTS: Out of the 2,261 articles screened, 29 articles were included in this systematic review and meta-analysis. The heterogeneity test indicated that there was heterogeneity among the included studies with no publication bias. The meta-analysis demonstrated that the total leukocyte count was significantly lower in patients with malaria (n = 4,619) than in those without malaria (n = 10,056) (Z = 4.0, P-value < 0.00001, mean difference = -1.38, 95% CI = -2.06-(-0.71)). Leukocyte differential alterations, low lymphocyte counts (P-value <0.0001, mean difference = -1.03, 95% CI = -1.53-(-0.53)) and a high NL ratio were found in the malaria group (n = 1,579) compared to the non-malaria group (n = 4,991) (P-value <0.0001, mean difference = 0.6, 95% CI = 0.32-0.88). The subgroup analysis indicated that there was a significantly lower total leukocyte count in the malaria group (n = 3,545) than in the febrile group (n = 8,947) (Z = 1.33, P-value < 0.0001, mean difference = -1.76, 95% CI = -2.56-(-0.96)), but no significant difference was found between the malaria group (n = 1,232) and the healthy group (n = 1,679) (P-value > 0.05). LIMITATIONS: As the specific diagnoses in the febrile groups were not reported in the included studies so that the results of the present study need to be carefully interpreted. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: This systematic review demonstrated that the total leukocyte count was affected by malarial infection at baseline despite the heterogeneity of the included studies. Future work must aim to understand the treatment-related total leukocyte reduction during follow-up or post-treatment outcomes in malaria-endemic settings.


Assuntos
Febre/sangue , Leucopenia/sangue , Malária/sangue , Humanos , Contagem de Leucócitos/métodos , Leucócitos/citologia
9.
Zhonghua Nei Ke Za Zhi ; 59(5): 372-374, 2020 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-32370466

RESUMO

To investigate the early changes of peripheral blood leukocyte differential counts in patients with COVID-19. Ten patients with COVID-19 and 30 patients with other viral pneumonia (non-COVID-19) admitted to The Sixth People's Hospital of Shanghai and Jinshan Branch Hospital from January 22 to February 17, 2020 were enrolled in this study. The differential counts of white blood cells (WBC) were analyzed. Patients in COVID-19 group showed relatively lower absolute WBC count 4.95(3.90,6.03)×10(9)/L, lymphocyte absolute count 1.20(0.98,1.50)×10(9)/L and eosinophil absolute count 0.01(0.01,0.01)×10(9)/L. Leukopenia developed in two patients(2/10), lymphocytopenia also in two patients(2/10). Seven over ten patients presented with eosinophil cytopenia. In non-COVID-19 group, absolute WBC count was 8.20(6.78,9.03)×10(9)/L (P<0.001), lymphocyte absolute count 1.75(1.20,2.53)×10(9)/L(P=0.036), eosinophil absolute count 0.02(0.01,0.03)×10(9)/L(P=0.005). Lymphocytopenia occurred in 16.7% patients, eosinophil cytopenia in 16.7% patients too. In conclusion, leukopenia, lymphocytopenia and eosinophil cytopenia are more common in COVID-19 patients than those in non-COVID-19 patients.


Assuntos
Infecções por Coronavirus/sangue , Leucócitos/citologia , Pneumonia Viral/sangue , Betacoronavirus , Estudos de Casos e Controles , China , Eosinófilos/citologia , Humanos , Contagem de Leucócitos , Leucopenia , Linfopenia , Pandemias
12.
Adv Exp Med Biol ; 1221: 435-444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32274720

RESUMO

Leukocyte migration is essential for exerting self-defense mechanisms. During the extravasation process, leukocytes transmigrate through the endothelial lining and the subendothelial basement membrane. Accumulating evidence supports the involvement of heparanase in this process. Altered cellular distribution resulting in relocalization of heparanase to the leading edge of migration is a key event to rapidly turn on the function of the enzyme during migration. This review presents current research investigating the cellular machinery that builds up a functional subcellular structure for leukocyte attachment to and degradation of the extracellular matrix. Recent advances in the understanding of the roles of heparanase in inflammatory diseases and pharmacological approaches to control heparanase-mediated actions during inflammation are also discussed.


Assuntos
Quimiotaxia de Leucócito , Glucuronidase/metabolismo , Leucócitos/citologia , Leucócitos/enzimologia , Matriz Extracelular , Humanos
13.
Sci Rep ; 10(1): 3982, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132598

RESUMO

Intracellular pathogens have evolved intricate mechanisms to subvert host cell signaling pathways and ensure their own propagation. A lineage of the protozoan parasite genus Theileria infects bovine leukocytes and induces their uncontrolled proliferation causing a leukemia-like disease. Given the importance of E2F transcription factors in mammalian cell cycle regulation, we investigated the role of E2F signaling in Theileria-induced host cell proliferation. Using comparative genomics and surface plasmon resonance, we identified parasite-derived peptides that have the sequence-specific ability to increase E2F signaling by binding E2F negative regulator Retinoblastoma-1 (RB). Using these peptides as a tool to probe host E2F signaling, we show that the disruption of RB complexes ex vivo leads to activation of E2F-driven transcription and increased leukocyte proliferation in an infection-dependent manner. This result is consistent with existing models and, together, they support a critical role of E2F signaling for Theileria-induced host cell proliferation, and its potential direct manipulation by one or more parasite proteins.


Assuntos
Fatores de Transcrição E2F/metabolismo , Leucócitos/citologia , Leucócitos/parasitologia , Transdução de Sinais , Theileria/fisiologia , Linhagem Celular , Proliferação de Células , Fator de Transcrição E2F1/metabolismo
14.
BMC Infect Dis ; 20(1): 205, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143599

RESUMO

BACKGROUND: The occurrence of segmental/lobar pattern pneumonia (S/L-PP) in children has recently increased. The pathogens of the disease may change for the misuse of antibiotics and the application of vaccines. Therefore, pathogens positive in hospitalized children with S/L-PP and their association with clinical characteristics may have changed. The aim of this study was to analyze the pathogens positive in hospitalized children with S/L-PP and their association with clinical characteristics. METHOD: The current study analyzed the epidemiological and clinical characteristics of pathogens positive in children with S/L-PP under 14 years old at a single hospital between 1st Jan 2014 and 31st Dec 2018 retrospectively. The pathogens were detected by microbial cultivation, indirect immunofluorescence of the kit (PNEUMOSLIDE IgM), Elisa, and/or real-time PCR in the samples of the patients. RESULTS: A total of 593 children with S/L-PP received treatment at a single hospital during the study period by inclusion criteria. Four hundred fifty-one patients were single positive for one pathogen and 83 patients were positive for at least 2 pathogens. Mycoplasma pneumoniae (M.pneumoniae) (72.34%) was the most commonly detected pathogen, followed by Streptococcus pneumoniae (S.pneumoniae) (8.77%). The prevalence of M.pneumoniae in children with S/L-PP increased with time (p < 0.05). The positive rate of M.pneumoniae increased with ages of patients (p < 0.05). M.pneumoniae was statistically associated with the extrapulmonary manifestations while S.pneumoniae was statistically associated with abnormal white blood cells (WBCs) and C reactive proteins (CRPs) (p < 0.05). CONCLUSION: M.pneumoniae was the most positive pathogen in children with S/L-PP. The positive rate of M.pneumoniae in children with S/L-PP increased with time and the ages of children. M.pneumoniae was associated with extrapulmonary manifestations while S.pneumoniae was associated with abnormal WBCs and CRPs.


Assuntos
Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/diagnóstico , Pneumonia Pneumocócica/diagnóstico , Streptococcus pneumoniae/isolamento & purificação , Adolescente , Proteína C-Reativa/análise , Criança , Criança Hospitalizada , Pré-Escolar , Feminino , Humanos , Lactente , Leucócitos/citologia , Masculino , Pneumonia por Mycoplasma/epidemiologia , Pneumonia Pneumocócica/epidemiologia , Prevalência , Estudos Retrospectivos , Estações do Ano
15.
PLoS One ; 15(3): e0229949, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182245

RESUMO

We present a two-tiered microchip system to capture and retrieve rare cells from blood samples with high purity. The first module of the system is a high throughput microfluidic interface that is used to immunomagnetically isolate targeted rare cells from whole blood, and discard > 99.999% of the unwanted leukocytes. The second module is a microwell array that furthers the purification by magnetically guiding each cell into a separate well concurrently, and allows individual retrieval of each cell. We demonstrate the design of the system as well as its characterization by experiments using model cell lines that represent circulating fetal trophoblasts. Our results show that single cells can be retrieved with efficiencies and purities as high as 100% within 145 mins.


Assuntos
Separação Celular , Procedimentos Analíticos em Microchip , Neoplasias/sangue , Análise de Célula Única , Linhagem Celular Tumoral , Humanos , Leucócitos/citologia , Análise em Microsséries , Microfluídica/métodos , Neoplasias/patologia , Trofoblastos/citologia
16.
Adv Exp Med Biol ; 1204: 197-214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32152948

RESUMO

Siglecs are sialic acid (Sia) recognizing immunoglobulin-like receptors expressed on the surface of all the major leukocyte lineages in mammals. Siglecs recognize ubiquitous Sia epitopes on various glycoconjugates in the cell glycocalyx and transduce signals to regulate immunological and inflammatory activities of these cells. The subset known as CD33-related Siglecs is principally inhibitory receptors that suppress leukocyte activation, and recent research has shown that a number of bacterial pathogens use Sia mimicry to engage these Siglecs as an immune evasion strategy. Conversely, Siglec-1 is a macrophage phagocytic receptor that engages GBS and other sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response, whereas certain viruses and parasites use Siglec-1 to gain entry to immune cells as a proximal step in the infectious process. Siglecs are positioned in crosstalk with other host innate immune sensing pathways to modulate the immune response to infection in complex ways. This chapter summarizes the current understanding of Siglecs at the host-pathogen interface, a field of study expanding in breadth and medical importance, and which provides potential targets for immune-based anti-infective strategies.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/imunologia , Animais , Glicocálix/imunologia , Humanos , Leucócitos/citologia , Leucócitos/imunologia , Macrófagos/imunologia , Fagocitose , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia
17.
Am J Sports Med ; 48(5): 1189-1199, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32134682

RESUMO

BACKGROUND: Tendinopathy is still a great challenge in clinical practice, and the role of platelet-rich plasma (PRP) is controversial. The influence of leukocytes on tendinopathy at an early stage has not been defined so far. PURPOSE: To compare the effects of leukocyte-rich PRP (Lr-PRP) and leukocyte-poor PRP (Lp-PRP) on Achilles tendinopathy when applied at an early stage. STUDY DESIGN: Controlled laboratory study. METHODS: A rabbit Achilles tendinopathy model was induced by a collagenase injection. A week later, treatments were applied randomly on local Achilles tendon lesions: (1) 200 µL of Lr-PRP (16 legs), (2) 200 µL of Lp-PRP (16 legs), and (3) 200 µL of saline (16 legs). At 3 and 6 weeks after the collagenase injection, outcomes were evaluated by histology, magnetic resonance imaging (MRI), real-time polymerase chain reaction analysis, immunohistochemistry, and transmission electron microscopy (TEM). RESULTS: The Lr-PRP group had a lower T2 signal intensity (P = .0377) and smaller diameter (P = .0193) and cross-sectional area (P = .0194) than the Lp-PRP group on MRI. Histologically, the Lr-PRP group had better scores than the Lp-PRP group (P = .0284 and P = .0188, respectively). Compared with the Lp-PRP group, higher gene expression and more protein synthesis of collagen I (P = .0160 and P = .0309, respectively) and CD163 (P < .0001 and P = .0411, respectively) were found in the Lr-PRP group. Considering TEM and biomechanical testing, the Lr-PRP group demonstrated more mature collagen fibers (P < .0001), a larger fiber diameter (P = .0005), a higher failure load (P = .00417), and higher tensile stress (P < .0001) than the Lp-PRP group. CONCLUSION: Lr-PRP had more beneficial effects than Lp-PRP when delivered at an early stage during tendon repair. CLINICAL RELEVANCE: Here, we showed that tendinopathy influenced the curative effects of PRP in vivo. An early-stage application of Lr-PRP had more benefits for the repair of tendinopathy than Lp-PRP in a rabbit model, which will supplement guidelines of PRP treatment on tendinopathy clinically.


Assuntos
Tendão do Calcâneo , Leucócitos/citologia , Plasma Rico em Plaquetas , Tendinopatia , Tendão do Calcâneo/diagnóstico por imagem , Animais , Colagenases , Coelhos , Tendinopatia/induzido quimicamente , Tendinopatia/diagnóstico por imagem , Tendinopatia/terapia
18.
Int J Mol Sci ; 21(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098334

RESUMO

Ezrin, radixin and moesin proteins (ERMs) are plasma membrane (PM) organizers that link the actin cytoskeleton to the cytoplasmic tail of transmembrane proteins, many of which are adhesion receptors, in order to regulate the formation of F-actin-based structures (e.g., microspikes and microvilli). ERMs also effect transmission of signals from the PM into the cell, an action mainly exerted through the compartmentalized activation of the small Rho GTPases Rho, Rac and Cdc42. Ezrin and moesin are the ERMs more highly expressed in leukocytes, and although they do not always share functions, both are mainly regulated through phosphatidylinositol 4,5-bisphosphate (PIP2) binding to the N-terminal band 4.1 protein-ERM (FERM) domain and phosphorylation of a conserved Thr in the C-terminal ERM association domain (C-ERMAD), exerting their functions through a wide assortment of mechanisms. In this review we will discuss some of these mechanisms, focusing on how they regulate polarization and migration in leukocytes, and formation of actin-based cellular structures like the phagocytic cup-endosome and the immune synapse in macrophages/neutrophils and lymphocytes, respectively, which represent essential aspects of the effector immune response.


Assuntos
Movimento Celular/fisiologia , Proteínas do Citoesqueleto/metabolismo , Leucócitos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Adesão Celular/fisiologia , Humanos , Leucócitos/citologia , Fagossomos/metabolismo
19.
Sci China Life Sci ; 63(3): 375-387, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32048161

RESUMO

Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines, selectins, addressins and other adhesion molecules derived from endothelial cells (ECs), but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive. In this study, using hepatic ischemia/reperfusion injury (HIRI) as a model, we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells (LSECs) in acute inflammation. In mice with EC-specific Notch activation (NICeCA), HIRI induced exacerbated liver damage. Consistently, endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor (TNF)-α expression in HIRI. Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin (EMCN), a negative regulator of leukocyte adhesion, was downregulated in LSECs from NICeCA mice. EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury. Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration, which was abrogated by EMCN overexpression in vitro. In mice deficient of RBPj, the integrative transcription factor of canonical Notch signaling, although overwhelming sinusoidal malformation aggravated HIRI, the expression of EMCN was upregulated; and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils. The Notch activation-exaggerated HIRI was compromised by blocking LFA-1, which mediated leukocyte adherence by associating with EMCN. Therefore, endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.


Assuntos
Moléculas de Adesão Celular/metabolismo , Neutrófilos/metabolismo , Traumatismo por Reperfusão/metabolismo , Sialomucinas/genética , Animais , Biópsia , Adesão Celular , Movimento Celular , Modelos Animais de Doenças , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Hepatócitos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sialomucinas/metabolismo , Distribuição Tecidual , Fator de Necrose Tumoral alfa/metabolismo
20.
Transfusion ; 60(3): 588-597, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32056228

RESUMO

BACKGROUND: Umbilical cord blood has become an important source of hematopoietic stem and progenitor cells for therapeutic applications. However, cord blood banking (CBB) grapples with issues related to economic viability, partially due to high discard rates of cord blood units (CBUs) that lack sufficient total nucleated cells for storage or therapeutic use. Currently, there are no methods available to assess the likelihood of CBUs meeting storage criteria noninvasively at the collection site, which would improve CBB efficiency and economic viability. MATERIALS AND METHODS: To overcome this limitation, we apply a novel label-free optical imaging method, called quantitative oblique back-illumination microscopy (qOBM), which yields tomographic phase and absorption contrast to image blood inside collection bags. An automated segmentation algorithm was developed to count white blood cells and red blood cells (RBCs) and assess hematocrit. Fifteen CBUs were measured. RESULTS: qOBM clearly differentiates between RBCs and nucleated cells. The cell-counting analysis shows an average error of 13% compared to hematology analysis, with a near-perfect, one-to-one relationship (slope = 0.94) and strong correlation coefficient (r = 0.86). Preliminary results to assess hematocrit also show excellent agreement with expected values. Acquisition times to image a statistically significant number of cells per CBU were approximately 1 minute. CONCLUSION: qOBM exhibits robust performance for quantifying blood inside collection bags. Because the approach is automated and fast, it can potentially quantify CBUs within minutes of collection, without breaching the CBUs' sterile environment. qOBM can reduce costs in CBB by avoiding processing expenses of CBUs that ultimately do not meet storage criteria.


Assuntos
Sangue Fetal/citologia , Leucócitos/citologia , Microscopia/métodos , Bancos de Sangue/estatística & dados numéricos , Doadores de Sangue/estatística & dados numéricos , Coleta de Amostras Sanguíneas , Humanos
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