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1.
Reprod Biomed Online ; 41(3): 365-369, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32565229

RESUMO

The question of whether SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus-2 [SARS-CoV-2], leading to the COVID-19 infection) can be harboured in the testes and/or semen is currently unanswered. It is essential to understand the limitations of both antibody and real-time PCR tests in interpreting SARS-CoV-2 data in relation to analyses of semen and testicular tissue without appropriate controls. This article critically analyses the evidence so far on this, and the possible implications. The limitations of diagnostic tests in both sampling and testing methodologies, their validation and their relevance in interpreting data are also highlighted.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/transmissão , Infertilidade Masculina/terapia , Pneumonia Viral/transmissão , Testículo/virologia , Infecções por Coronavirus/diagnóstico , Humanos , Masculino , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/diagnóstico , RNA Viral/análise , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/metabolismo , Sêmen/virologia , Serina Endopeptidases/análise , Serina Endopeptidases/metabolismo , Espermatozoides/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Doadores de Tecidos
2.
Scand J Immunol ; 92(1): e12889, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32299134

RESUMO

The analysis of tumour-associated macrophages (TAMs) has a high potential to predict cancer recurrence and response to immunotherapy. However, the heterogeneity of TAMs poses a challenge for quantitative and qualitative measurements. Here, we critically evaluated by immunohistochemistry and flow cytometry two commonly used pan-macrophage markers (CD14 and CD68) as well as some suggested markers for tumour-promoting M2 macrophages (CD163, CD204, CD206 and CD209) in human non-small cell lung cancer (NSCLC). Tumour, non-cancerous lung tissue and blood were investigated. For immunohistochemistry, CD68 was confirmed to be a useful pan-macrophage marker although careful selection of antibody was found to be critical. The widely used anti-CD68 antibody clone KP-1 stains both macrophages and neutrophils, which is problematic for TAM quantification because lung tumours contain many neutrophils. For TAM counting in tumour sections, we recommend combined labelling of CD68 with a cell membrane marker such as CD14, CD163 or CD206. In flow cytometry, the commonly used combination of CD14 and HLA-DR was found to not be optimal because some TAMs do not express CD14. Instead, combined staining of CD68 and HLA-DR is preferable to gate all TAMs. Concerning macrophage phenotypic markers, the scavenger receptor CD163 was found to be expressed by a substantial fraction (50%-86%) of TAMs with a large patient-to-patient variation. Approximately 50% of TAMs were positive for CD206. Surprisingly, there was no clear overlap between CD163 and CD206 positivity, and three distinct TAM sub-populations were identified in NSCLC tumours: CD163+ CD206+ , CD163+ CD206- and CD163- CD206- . This work should help develop macrophage-based prognostic tools for cancer.


Assuntos
Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Receptores de Lipopolissacarídeos/análise , Neoplasias Pulmonares/diagnóstico , Macrófagos Alveolares/imunologia , Receptores de Superfície Celular/análise , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Moléculas de Adesão Celular/análise , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Lectinas Tipo C/análise , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Lectinas de Ligação a Manose/análise , Prognóstico , Receptores Depuradores Classe A/análise
3.
Medicine (Baltimore) ; 99(17): e19839, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332633

RESUMO

The present study was designed to investigate the expression of tumor-associated macrophages (TAMs) in gastric cancer and its clinicopathological relationship. In addition, we also aimed to analyze the relationship between helicobacter pylori (HP) infection and TAMs in gastric cancer.The protein expression of CD16 and CD163 in 90 gastric cancer tissues and 30 margin tissues was detected by immunohistochemistry. HP infection was detected in 90 gastric cancer tissues and 30 margin tissues by gram staining and immunohistochemistry.There was no clear correlation between CD16 macrophages and gastric cancer. The density of CD163 macrophages was not correlated with the general condition of tumor patients, but with tumor size, tumor differentiation, lymphatic metastasis, depth of invasion and TNM stage. Additionally, the infection rate of HP in gastric cancer tissues was significantly higher.In summary, TAMs are associated with tumor size, degree of differentiation, depth of invasion, lymph node metastasis and TNM stage, suggesting their critical role in the invasion and metastasis of gastric cancer.


Assuntos
Macrófagos/patologia , Neoplasias Gástricas/patologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Contagem de Células , Feminino , Proteínas Ligadas por GPI/análise , Mucosa Gástrica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Receptores de Superfície Celular/análise , Receptores de IgG/análise , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Carga Tumoral
4.
Cell Mol Life Sci ; 77(6): 1087-1101, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31598735

RESUMO

The insect gustatory system senses taste information from environmental food substrates and processes it to control feeding behaviors. Drosophila melanogaster has been a powerful genetic model for investigating how various chemical cues are detected at the molecular and cellular levels. In addition to an understanding of how tastants belonging to five historically described taste modalities (sweet, bitter, acid, salt, and amino acid) are sensed, recent findings have identified taste neurons and receptors that recognize tastants of non-canonical modalities, including fatty acids, carbonated water, polyamines, H2O2, bacterial lipopolysaccharide (LPS), ammonia, and calcium. Analyses of response profiles of taste neurons expressing different suites of chemosensory receptors have allowed exploration of taste coding mechanisms in primary sensory neurons. In this review, we present the current knowledge of the molecular and cellular basis of taste detection of various categories of tastants. We also summarize evidence for organotopic and multimodal functions of the taste system. Functional characterization of peripheral taste neurons in different organs has greatly increased our understanding of how insect behavior is regulated by the gustatory system, which may inform development of novel insect pest control strategies.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/fisiologia , Receptores de Superfície Celular/metabolismo , Células Receptoras Sensoriais/metabolismo , Paladar , Animais , Drosophila/anatomia & histologia , Drosophila/citologia , Drosophila/genética , Proteínas de Drosophila/análise , Proteínas de Drosophila/genética , Expressão Gênica , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/genética , Células Receptoras Sensoriais/citologia
5.
BMC Infect Dis ; 19(1): 1006, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779590

RESUMO

BACKGROUND: Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis. METHODS: We enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay. RESULTS: Higher frequency of CD14+CD16+ (15.7% vs 7.8%, P < 0.0001) and CD14-CD16+ (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14+CD16- (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163+ cells in CD16+ monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment. CONCLUSIONS: Higher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.


Assuntos
Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Monócitos/metabolismo , Receptores de Superfície Celular/análise , Tuberculose/diagnóstico , Adulto , Idoso , Antígenos CD/sangue , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos de Diferenciação Mielomonocítica/metabolismo , Área Sob a Curva , Estudos de Casos e Controles , Feminino , Humanos , Imunidade Inata , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/imunologia , Prognóstico , Curva ROC , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/metabolismo , Receptores de IgG/metabolismo , Índice de Gravidade de Doença , Tuberculose/imunologia , Tuberculose/patologia , Tuberculose Pleural/imunologia , Tuberculose Pleural/patologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia
6.
Food Funct ; 10(12): 7818-7827, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31696193

RESUMO

Human milk provides a range of nutrients and bioactive components, which can support the growth and development of infants. However, human milk composition may change due to geographic and ethnic variation. This study investigated the variation of the Chinese human milk serum proteome based on mothers with different ethnicities living in different parts of China, using TMT labeling combined with Nano-LC Q Exactive HF MS/MS proteomics. In total, 693 proteins were identified and quantified in human milk serum from Yunnan (Han and Bai ethnicity), Gansu (Han and Tibetan ethnicity), Xinjiang (Uygur ethnicity), and Inner Mongolia (Mongolian ethnicity). The biological function distribution of identified proteins and the summed intensity of proteins belonging to each biological function were similar among groups. The five relatively highly abundant milk serum proteins, lactoferrin, serum albumin, polymeric immunoglobulin receptor, macrophage mannose receptor 1, and bile salt-activated lipase were not significantly different among different geographies and ethnicities. On the other hand, we found 34 proteins that did significantly differ with geography and ethnicity. Those significantly different proteins have known strong interaction in inflammation response and regulation of multi-organism processes. Taken together, biological function distribution was similar on both the qualitative and quantitative levels, and proteins with similar abundance are important in providing basic nutrition and protection for infants, whereas the significantly different proteins may be important for the healthy development of infants from different locations and ethnicities.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Leite Humano/química , China/etnologia , Grupos Étnicos , Feminino , Humanos , Lactação , Lactoferrina/análise , Lectinas Tipo C/análise , Lectinas de Ligação a Manose/análise , Proteoma/química , Receptores de Superfície Celular/análise , Albumina Sérica/análise , Espectrometria de Massas em Tandem
7.
Aerosp Med Hum Perform ; 90(12): 1050-1054, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748002

RESUMO

BACKGROUND: In the last 10 yr, the number of ultra-haul flights-defined as flights greater than 12 h of flying time-has increased. While the medical complications of these flights are well-known, the underlying cellular effects are less clear. The primary objective of this study was to test the effects of extended mild hypobaric hypoxia on overall well-being and skeletal muscle morphology and macrophage populations.METHODS: A total of 22 male C57BL/6 mice were assigned to a normobaric (NB) or hypobaric (HB) chamber for 14-17 h. Overall mouse well-being and the general morphology and resident macrophage number in hindlimb muscles were compared between the two pressure conditions.RESULTS: During mild hypobaric hypoxia, the mice behaved normally and no changes were observed in general muscle morphology. Regarding resident macrophages, the mean antigen area of CD206 in the hindlimb muscles, lateral gastrocnemius (LG, 33.8 ± 2.0 vs. 35.3 ± 1.6), medial gastrocnemius (MG, 32.4 ± 1.6 vs. 32.6 ± 1.5), and quadriceps femoris (QF, 36.3 ± 1.2 vs. 34.3 ± 1.1) were similar between NB and HB conditions, and the number of CD68-positive cells in the LG and QF were similar between the two conditions. Significantly fewer CD206-positive cells were counted in the LG muscle under the HB condition.CONCLUSION: Our findings indicate that extended exposure to mild hypobaric hypoxia, similar to that of an ultra-long-haul flight, does not adversely affect healthy skeletal muscle.Zhang L, Soulakova J, St. Pierre Schneider B. Mild hypobaric hypoxia effects on murine skeletal muscle morphology and macrophages and well-being. Aerosp Med Hum Perform. 2019; 90(12):1050-1054.


Assuntos
Altitude , Hipóxia/fisiopatologia , Macrófagos , Músculo Esquelético , Oxigênio/farmacologia , Animais , Comportamento Animal , Lectinas Tipo C/análise , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Lectinas de Ligação a Manose/análise , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Receptores de Superfície Celular/análise
8.
Cancer Immunol Immunother ; 68(10): 1597-1603, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31520110

RESUMO

BACKGROUND: Despite the promise of immunotherapy for gastric adenocarcinoma, choices for the selection of effective antigenic targets are very limited. Previously published data and our own in-house computational analysis have suggested that ANTXR1 is a potential target, simultaneously expressed in malignant tumor cells and the endothelial cells of the tumors. However, the expression pattern of ANTXR1 protein in clinical samples of gastric adenocarcinoma has not been fully evaluated. METHODS: Using immunohistochemistry (IHC), we recorded the percentage of ANTXR1 positive cells separately in tumor cells and endothelial cells in the primary tumor, non-tumor gastric tissue adjacent to the primary tumor, and tumor in metastatic sites of 140 gastric adenocarcinoma patients. We also evaluated the association of ANTXR1 expression with the Lauren histological classification of the primary tumors, the patient's history of neoadjuvant chemotherapy and/or radiotherapy, and the patient's overall survival. RESULTS: ANTXR1 was expressed in a mean of 73.89 ± 30.12% of tumor cells and 13.55 ± 20.53% of endothelial cells in the primary tumors. Intestinal adenocarcinomas had lower ANTXR1 expression in the tumor cells and higher ANTXR1 expression in the endothelial cells of the tumor regions, and a history of neoadjuvant therapy was associated with increased ANTXR1 expression in the endothelial cells of the tumor regions. Finally, above median expression of ANTXR1 in the tumor cells of the tumor regions was associated with significantly lower overall patient survival. CONCLUSIONS: Our findings suggest that ANTXR1 is a promising candidate for preclinical and clinical evaluation for gastric adenocarcinoma immunotherapy.


Assuntos
Adenocarcinoma/terapia , Proteínas de Neoplasias/análise , Receptores de Superfície Celular/análise , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Endoteliais/química , Feminino , Humanos , Imuno-Histoquímica , Imunoterapia , Masculino , Proteínas dos Microfilamentos , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade
9.
Crit Care ; 23(1): 270, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375142

RESUMO

BACKGROUND: Invasive fungal infections (IFI) are difficult to diagnose, especially in critically ill patients. As the mannose receptor (MR) is shed from macrophage cell surfaces after exposure to fungi, we investigate whether its soluble serum form (sMR) can serve as a biomarker of IFI. METHODS: This is a secondary analysis of the multicentre randomised controlled trial (EPaNIC, n = 4640) that investigated the impact of initiating supplemental parenteral nutrition (PN) early during critical illness (Early-PN) as compared to withholding it in the first week of intensive care (Late-PN). Serum sMR concentrations were measured in three matched patient groups (proven/probable IFI, n = 82; bacterial infection, n = 80; non-infectious inflammation, n = 77) on the day of antimicrobial initiation or matched intensive care unit day and the five preceding days, as well as in matched healthy controls (n = 59). Independent determinants of sMR concentration were identified via multivariable linear regression. Serum sMR time profiles were analysed with repeated-measures ANOVA. Predictive properties were assessed via area under the receiver operating curve (aROC). RESULTS: Serum sMR was higher in IFI patients than in all other groups (all p < 0.02), aROC to differentiate IFI from no IFI being 0.65 (p < 0.001). The ability of serum sMR to discriminate infectious from non-infectious inflammation was better with an aROC of 0.68 (p < 0.001). The sMR concentrations were already elevated up to 5 days before antimicrobial initiation and remained stable over time. Multivariable linear regression analysis showed that an infection or an IFI, higher severity of illness and sepsis upon admission were associated with higher sMR levels; urgent admission and Late-PN were independently associated with lower sMR concentrations. CONCLUSION: Serum sMR concentrations were higher in critically ill patients with IFI than in those with a bacterial infection or with non-infectious inflammation. However, test properties were insufficient for diagnostic purposes.


Assuntos
Infecções Bacterianas/diagnóstico , Inflamação/diagnóstico , Infecções Fúngicas Invasivas/diagnóstico , Lectinas Tipo C/análise , Lectinas de Ligação a Manose/análise , Receptores de Superfície Celular/análise , Idoso , Análise de Variância , Infecções Bacterianas/sangue , Biomarcadores/análise , Biomarcadores/sangue , Estado Terminal/epidemiologia , Estado Terminal/terapia , Feminino , Humanos , Inflamação/sangue , Infecções Fúngicas Invasivas/sangue , Lectinas Tipo C/sangue , Masculino , Lectinas de Ligação a Manose/sangue , Pessoa de Meia-Idade , Curva ROC , Receptores de Superfície Celular/sangue , Fatores de Tempo
10.
Med Hypotheses ; 131: 109281, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443770

RESUMO

The data of literature are discordant about the role of mast cells in different types of neoplasms. In this paper the authors propose the hypothesis that tumor-associated mast cells may switch to different polarization states, conditioning the immunogenic capacities of the different neoplasms. Anti-inflammatory polarized mast cells should express cytokines such as interleukin-10 (IL-10) and then mast cells number should be inversely related to the intensity of inflammatory infiltrate. On the contrary, when mast cells do not express anti-inflammatory cytokines their number should be directly related to the intensity of the inflammatory infiltrate. In this paper we briefly argue around feasible approaches, based on the retrospective studies of tumor tissue samples from neoplasms considered "immunologically hot" and neoplasms considered "immunologically cold", through immunohistochemistry and immunofluorescence techniques (confocal microscopy). The establishment of the actual existence of a polarization interchange of mast cells, could lead to a new vision in prognostic terms, useful to contrive new approaches in immunotherapy of tumors.


Assuntos
Citocinas/biossíntese , Mastócitos/imunologia , Modelos Imunológicos , Neoplasias/imunologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos de Neoplasias/análise , Contagem de Células , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoquímica , Inflamação , Linfócitos do Interstício Tumoral/química , Macrófagos/química , Mastócitos/metabolismo , Mastócitos/ultraestrutura , Microscopia Confocal , Neoplasias/química , Neoplasias/ultraestrutura , Inclusão em Parafina , Proteínas Proto-Oncogênicas c-kit/análise , Receptores de Superfície Celular/análise , Projetos de Pesquisa , Estudos Retrospectivos
12.
Gastroenterol Hepatol ; 42(9): 534-541, 2019 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31326104

RESUMO

INTRODUCTION AND AIM: Thromboxane (TX) A2 was identified as an important vasoconstrictor during Zymosan induced portal perfusion pressure (PP) increase. We aimed at investigating whether hepatic steatosis influences the extent of TXA2-induced portal hypertension. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control and steatosis (induced by the special diet) groups. PP and TXB2 (stable degradation product of TXA2) in the perfusate were measured after in situ liver perfusion with Zymosan (150µg/ml, 40-46min) or U46619 (TXA2 analog, 0.1µM/ml, 40-46min). The number of Kupffer cell (KC) was measured by immunohistochemistry with CD163. RESULTS: Zymosan induced more TXB2 production and a higher PP increase in control group than in steatosis group despite more CD163 positive KCs in fatty livers. PP and TXB2 efflux revealed a strong correlation in control group and a moderate correlation in steatosis group. Contrary to the effect of Zymosan, U46619 induced a much higher PP increase in steatosis group than in control group. CONCLUSION: Severe steatosis increased number of KCs, however, PP increase and TXB2 efflux caused by Zymosan infusion in fatty livers were lower than those in healthy livers. In contrast, TXA2 analog caused higher PP increase in fatty livers. Targeting the more sensitive response to TXA2 in fatty livers might be a potential therapy of severe steatosis.


Assuntos
Fígado Gorduroso/complicações , Hipertensão Portal/induzido quimicamente , Pressão na Veia Porta/efeitos dos fármacos , Tromboxano B2/biossíntese , Zimosan/farmacologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Animais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Contagem de Células , Dieta Hiperlipídica , Fígado Gorduroso/patologia , Fígado Gorduroso/fisiopatologia , Macrófagos do Fígado/química , Macrófagos do Fígado/citologia , Perfusão/métodos , Pressão na Veia Porta/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular/análise , Tromboxano A2/análogos & derivados , Tromboxano B2/análise , Vasoconstritores
13.
Arterioscler Thromb Vasc Biol ; 39(9): 1762-1775, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31315440

RESUMO

OBJECTIVE: Atherosclerotic cardiovascular disease (ASCVD) is an increasing cause of morbidity and mortality in people with HIV since the introduction of combination antiretroviral therapy. Despite recent advances in our understanding of HIV ASCVD, controversy still exists on whether this increased risk of ASCVD is due to chronic HIV infection or other risk factors. Mounting biomarker studies indicate a role of monocyte/macrophage activation in HIV ASCVD; however, little is known about the mechanisms through which HIV infection mediates monocyte/macrophage activation in such a way as to engender accelerated atherogenesis. Here, we experimentally investigated whether HIV expression is sufficient to accelerate atherosclerosis and evaluated the role of caspase-1 activation in monocytes/macrophages in HIV ASCVD. Approach and Results: We crossed a well-characterized HIV mouse model, Tg26 mice, which transgenically expresses HIV-1, with ApoE-/- mice to promote atherogenic conditions (Tg26+/-/ApoE-/-). Tg26+/-/ApoE-/- have accelerated atherosclerosis with increased caspase-1 pathway activation in inflammatory monocytes and atherosclerotic vasculature compared with ApoE-/-. Using a well-characterized cohort of people with HIV and tissue-banked aortic plaques, we documented that serum IL (interleukin)-18 was higher in people with HIV compared with non-HIV-infected controls, and in patients with plaques, IL-18 levels correlated with monocyte/macrophage activation markers and noncalcified inflammatory plaques. In autopsy-derived aortic plaques, caspase-1+ cells and CD (clusters of differentiation) 163+ macrophages correlated. CONCLUSIONS: These data demonstrate that expression of HIV is sufficient to accelerate atherogenesis. Further, it highlights the importance of caspase-1 and monocyte/macrophage activation in HIV atherogenesis and the potential of Tg26+/-/ApoE-/- as a tool for mechanistic studies of HIV ASCVD.


Assuntos
Aterosclerose/etiologia , Caspase 1/fisiologia , Infecções por HIV/complicações , Animais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Apolipoproteínas E/fisiologia , Estudos de Coortes , Modelos Animais de Doenças , Ativação Enzimática , Feminino , Interleucina-18/sangue , Masculino , Camundongos , Camundongos Transgênicos , Receptores de Superfície Celular/análise
14.
Braz Oral Res ; 33: e047, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31141038

RESUMO

The aim of this study was to evaluate macrophage M1 and M2 subpopulations in radicular cysts (RCs) and periapical granulomas (PGs) and relate them to clinical and morphological aspects. M1 macrophages were evaluated by the percentage of CD68 immunostaining associated with the inflammatory cytokine TNF-α, and M2 macrophages, by its specific CD163 antibody. The CD68+/CD163+ ratio was adopted to distinguish between the two macrophage subpopulations. Clinical, radiographic, symptomatology, treatment, and morphological parameters of lesions were collected and a significance level of p = 0.05 was adopted for statistical analysis. The results showed that the CD68+/CD163+ ratio was higher in the RCs (median = 1.22, p = 0.002), and the highest TNF-α immunostaining scores were found in RCs (p = 0.018); in PGs, the CD68+/CD163+ ratio was lower and associated with a greater CD163+ immunostaining (median = 1.02, p <0.001). The TNF-α in cyst epithelium had a score of 3 in 10 cases and predominance of M1 macrophages by CD68+/CD163+ (median = 2.23). In addition, CD68+ cells had higher percentage of immunostaining in smaller RCs (p = 0.034). Our findings suggest that increased CD68 immunostaining associated with TNF-α cytokine in RCs results in a greater differentiation of the M1 phenotype. The higher CD163 immunostaining in PGs results in greater differentiation of the M2 phenotype. Therefore, the inflammatory state promoted by M1 macrophages is related to growth and progression of RCs; on the other hand, the immunomodulatory state of M2 macrophages is related to maintenance of PGs.


Assuntos
Macrófagos/patologia , Granuloma Periapical/patologia , Cisto Radicular/patologia , Adulto , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Doença Crônica , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/análise , Valores de Referência , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/análise
15.
Clin Exp Metastasis ; 36(4): 351-363, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31119444

RESUMO

The infiltration of tumor-associated macrophages (TAMs) is associated with tumor progression and poor prognosis in endometrial cancer (EC). Collagen triple helix repeat containing 1 (CTHRC1), a secreted ECM protein, has been reported to have important roles in promoting cancer invasion and metastasis, but the functional role of CTHRC1 and its association with TAMs in EC remain unclear. Here we report that, in EC patients, CTHRC1 expression was up-regulated in endometrial cancer tissues compared with normal endometrium (P < 0.0001), and is positively correlated with tumor grade and depth of myometrial invasion (P = 0.024 and P = 0.0002, respectively). Meanwhile, CTHRC1 expression was positively correlated with an increased number of infiltrating TAMs, especially M2-like TAMs (P = 0.003, P = 0.001). In the tumor microenvironment of EC, CTHRC1 not only promoted myometrial invasion by interacting with Integrin ß3-Akt signaling pathway, but also promoted infiltration of M2-like TAMs by upregulating Fractalkine chemokine receptor (CX3CR1) expression in macrophages. Changing levels of recombinant CTHRC1 protein (rCTHRC1) promoted tumor migration and invasion via enhancing macrophage recruitment in vitro. In summary, our findings eventually provided a novel role for CTHRC1 in remodeling the tumor immune microenvironment to promote tumor metastasis in EC patients.


Assuntos
Neoplasias do Endométrio/patologia , Proteínas da Matriz Extracelular/fisiologia , Integrina beta3/fisiologia , Macrófagos/fisiologia , Miométrio/patologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Linhagem Celular Tumoral , Movimento Celular , Neoplasias do Endométrio/imunologia , Feminino , Humanos , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/fisiologia , Receptores de Superfície Celular/análise , Transdução de Sinais/fisiologia , Microambiente Tumoral
16.
Endocr Pathol ; 30(2): 90-95, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31001800

RESUMO

We describe a consistently present, previously unrecognized, population of monocytes in pheochromocytomas and paragangliomas. Although sustentacular cells are generally recognized as a common component of these tumors, differential immunohistochemical staining for CD163 and S100 shows that monocytes can in fact be more numerous. These cells frequently resemble sustentacular cells topographically and cytologically, possibly explaining why they have not been previously noticed. They contribute to the tumor proteome and may have implications for tumor biology. No correlations were identifiable between the presence of these cells and any clinical characteristics of the tumors in the present study. A possible association with genotype is suggested by immunoblot showing high expression of CD163 protein in tumors with succinate dehydrogenase mutations.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Monócitos/patologia , Paraganglioma/patologia , Feocromocitoma/patologia , Neoplasias das Glândulas Suprarrenais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação/genética , Paraganglioma/genética , Feocromocitoma/genética , Receptores de Superfície Celular/análise , Proteínas S100/análise , Succinato Desidrogenase/genética
17.
J Agric Food Chem ; 67(7): 1902-1917, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30663306

RESUMO

Bovine colostrum is a rich source of bioactive components which are important in the development of the intestine, in stimulating gut structure and function and in preparing the gut surface for subsequent colonization of microbes. What is not clear, however, is how colostrum may affect the repertoire of receptors and membrane proteins of the intestinal surface and the post-translational modifications associated with them. In the present work, we aimed to characterize the surface receptor and glycan profile of human HT-29 intestinal cells after exposure to a bovine colostrum fraction (BCF) by means of proteomic and glycomic analyses. Integration of label-free quantitative proteomic analysis and lectin array profiles confirmed that BCF exposure results in changes in the levels of glycoproteins present at the cell surface and also changes to their glycosylation pattern. This study contributes to our understanding of how milk components may regulate intestinal cells and prime them for bacterial interaction.


Assuntos
Colostro/fisiologia , Enterócitos/química , Glicômica/métodos , Proteômica/métodos , Animais , Bovinos , Colostro/química , Feminino , Glicoproteínas/análise , Células HT29 , Humanos , Lectinas/análise , Polissacarídeos/análise , Receptores de Superfície Celular/análise
18.
J Immunol ; 202(5): 1635-1643, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683706

RESUMO

CD163 facilitates regulation and resolution of inflammation and removal of free hemoglobin and is highly expressed in myeloid cells from patients with inflammatory disorders, such as systemic juvenile idiopathic arthritis (SJIA) and macrophage activation syndrome (MAS). Our recent studies indicate that regulation of CD163 mRNA expression is a key functional property of polarized monocytes and macrophages and is mediated at the transcriptional and posttranscriptional level, including via microRNAs. The goal of the current study is to develop a multiparameter flow cytometry panel incorporating detection of CD163 mRNA for polarized monocyte and macrophage populations in disorders such as SJIA and MAS. THP-1 cells and CD14+ human monocytes were stained using fluorochrome-conjugated Abs to myeloid surface markers, along with CD163 mRNA. Staining for mRNA could reliably detect CD163 expression while simultaneously detecting different macrophage populations using Abs targeting CD14, CD64, CD80, CD163, and CD209. This approach was found to be highly sensitive for increased mRNA expression when macrophages were polarized with IL-10 [M(IL-10)], with a strong signal over a broad range of IL-10 concentrations, and showed distinct kinetics of CD163 mRNA and protein induction upon IL-10 stimulation. Finally, this panel demonstrated clear changes in polarization markers in unstimulated monocytes from patients with SJIA and MAS, including upregulated CD163 mRNA and increased CD64 expression. This approach represents a robust and sensitive system for RNA flow cytometry, useful for studying CD163 expression as part of a multimarker panel for human monocytes and macrophages, with broad applicability to the pathogenesis of hyperinflammatory diseases.


Assuntos
Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Citometria de Fluxo , Inflamação/imunologia , Macrófagos/imunologia , Monócitos/imunologia , RNA Mensageiro/análise , Receptores de Superfície Celular/análise , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/imunologia , Células Cultivadas , Humanos , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia
19.
Environ Int ; 123: 535-542, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30622078

RESUMO

Ambient fine particulate matter (PM2.5) is a risk factor for respiratory diseases. Previous studies suggest that PM2.5 exposure may down-regulate airway antimicrobial proteins and peptides (AMPs), thereby accelerating airway pathogen infection. However, epidemiological research is scarce. Hence, we estimated the associations between individual PM2.5 chronic daily intake (CDI) and the levels of the airway AMP salivary agglutinin (SAG), as well as peripheral leukocyte counts and pro-inflammatory cytokines, of preschool children in Guiyu (an e-waste area) and Haojiang (a reference area located 31.6 km to the east of Guiyu). We recruited 581 preschool children from Guiyu and Haojiang, of which 222 were included in this study for a matching design (Guiyu: n = 110 vs. Haojiang: n = 112). Air PM2.5 pollution data was collected to calculate individual PM2.5 CDI. The mean concentration of PM2.5 in Guiyu was higher than in Haojiang, resulting in a higher individual PM2.5 CDI. Concomitantly, saliva SAG levels were lower in Guiyu children (5.05 ng/mL) than in Haojiang children (8.68 ng/mL), and were negatively correlated with CDI. Additionally, peripheral counts of white blood cells, and the concentrations of interleukin-8 and tumor necrosis factor-alpha, in Guiyu children were greater than in Haojiang children, and were positively associated with CDI. Similar results were found for neutrophils and monocytes. To our knowledge, this is the first study on the relationship between PM2.5 exposure and innate airway antimicrobial activity in children, in an e-waste area, showing that PM2.5 pollution may weaken airway antimicrobial activity by down-regulation of saliva SAG levels, which might accelerate airway pathogen infection in children.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Resíduo Eletrônico/efeitos adversos , Material Particulado/toxicidade , Proteína D Associada a Surfactante Pulmonar/sangue , Receptores de Superfície Celular/análise , Poluentes Atmosféricos/efeitos adversos , Criança , Pré-Escolar , Citocinas/sangue , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Leucócitos , Masculino , Infecções Respiratórias/induzido quimicamente , Infecções Respiratórias/imunologia , Fatores de Risco
20.
Cell Immunol ; 336: 75-82, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30665661

RESUMO

Obesity is seen as a low grade inflammatory state, and is associated with adverse pregnancy outcomes. Disturbed macrophage characteristics might be essential in obesity associated pregnancy pathology via effects on the regulation of angiogenesis and placental development. This study aims to address the effects of maternal obesity on macrophage subsets in the decidua of women with term uncomplicated pregnancies. Macrophages were isolated from the decidua basalis and decidua parietalis of women with pre-gravid BMI < 25 (control) and BMI > 30 (obese). Macrophages were characterized and quantified using multi-color flow cytometry. Placentas of 10 obese and 10 control women after an uncomplicated term pregnancy were included. The decidua parietalis, but not decidua basalis, showed significantly lower levels of M1-type (HLA-DR+, CD163-) macrophages (p < 0.05) in obese women (4,3% of total macrophages) compared to control women (5,3% of total macrophages). The lower levels of M1 macrophages, considered to be pro-inflammatory, might indicate a mechanism to compensate for the pro-inflammatory environment in obese women to ensure healthy pregnancy outcomes.


Assuntos
Decídua/imunologia , Macrófagos/classificação , Obesidade Materna/imunologia , Adulto , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Feminino , Antígenos HLA-DR/análise , Humanos , Gravidez , Receptores de Superfície Celular/análise
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