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1.
Adv Exp Med Biol ; 1175: 335-353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583594

RESUMO

Microglia are the most abundant immune cells in the central nervous system (CNS), where they interact with neurons and exhibit a wide array of functions in physiological and pathological conditions. Physiologically, microglia mediate synaptic pruning and remodeling crucial for neural circuits and brain connectivity. In pathological conditions such as neurodegeneration in the Parkinson's disease (PD), microglia are activated, migrated to the injury site, and prone to engulf debris, sense pathology, and secrete possible pro- and anti-inflammatory factors. Microglia mediate responses such as inflammation and phagocytosis associated with neurodegeneration and are pivotal players in exacerbating or relieving disease progression. This chapter provides an overview on microglial function in the neurodegenerative disease-Parkinson's disease (PD). An overview on the pathology of PD will first be given, followed by discussion on receptors and signaling pathways involved in microglia-mediated inflammation and phagocytosis. Mechanism of how microglia contribute to PD by inflammation, phagocytosis of α-Synuclein (α-Syn), and interaction with PD genes will also be discussed.


Assuntos
Microglia/citologia , Doença de Parkinson/fisiopatologia , Humanos , Inflamação/fisiopatologia , Fagocitose , Transdução de Sinais , alfa-Sinucleína
2.
Mem Inst Oswaldo Cruz ; 114: e190158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596312

RESUMO

As phagocytosis is the first line of defense against malaria, we developed a phagocytosis assay with Plasmodium vivax (P. vivax) merozoites that can be applied to evaluate vaccine candidates. Briefly, after leukocyte removal with loosely packed cellulose powder in a syringe, P. vivax trophozoites matured to the merozoite-rich schizont stages in the presence of the E64 protease inhibitor. The Percoll gradient-enriched schizonts were chemically disrupted to release merozoites that were submitted to merozoite opsonin-dependent phagocytosis in two phagocytic lines with human and mouse antibodies against the N- and C-terminus of P. vivax Merozoite Surface Protein-1 (Nterm-PvMSP1 and MSP119). The resulting assay is simple and efficient for use as a routine phagocytic assay for the evaluation of merozoite stage vaccine candidates.


Assuntos
Anticorpos Antiprotozoários/imunologia , Merozoítos/imunologia , Fagocitose/fisiologia , Plasmodium vivax/imunologia , Proteínas de Protozoários/imunologia , Animais , Feminino , Citometria de Fluxo , Merozoítos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium vivax/fisiologia
3.
Cell Host Microbe ; 26(4): 450-452, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600498

RESUMO

Bacteriophages, viruses that infect bacteria, are the most abundant biological entities within the holobiont. In this issue of Cell Host & Microbe, Jahn et al. (2019) describe a group of phages that can suppress immune cell function in marine sponges using secreted ankyrin proteins. They call these phages Ankyphages.


Assuntos
Bacteriófagos , Eucariotos , Bactérias , Evasão da Resposta Imune , Fagocitose , Prófagos
4.
Aquat Toxicol ; 215: 105284, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31479758

RESUMO

Metal pollution in the environment is a serious threat to the biological sustainability of coastal ecosystems. However, our current understanding of the biological effects of metals in these ecosystems is limited. Herein, we investigated the responses of the sea slug Onchidium reevesii to persistent sublethal Cd environmental stress. Dynamic expression was analyzed using various biomarkers. The full-length cDNA of O. reevesii metallothionein (MT) was cloned and consists of 1639 nucleotides encoding a 65 amino acid polypeptide. Phylogenetic analysis showed that Or-MT has conserved Cys residues typical of MTs, including a typical Cys-X-Cys motif, implying that it can function the same as the MT of other shellfish. Expression of Or-MT in response to Cd varied in different tissues, and was highest in gastropod tissues. Thus, regiotemporal expression of MT may be useful for assessing pollution in coastal areas. Cellular immunity (in the hemolymph) and enzyme activity (in the hepatopancreas) were investigated along with hemocyte viability, hemocyte phagocytosis, and superoxide dismutase (SOD) and aspartate aminotransferase (AST) activities. Hemocyte viability was elevated under continuous Cd exposure but hemocyte phagocytosis was decreased. SOD and AST activities in the hepatopancreas fluctuated considerably, and SOD activity was more sensitive. SOD activity was lowest at 4 h and highest at 12 h, while AST activity peaked at 2 h and was lowest at 48 h. Thus, changes in enzyme activity may reveal adaptation to stress. Furthermore, the response patterns of certain enzymes, cellular immunity, and MT expression in O. reevesii could serve as biomarkers of Cd pollution in aquatic environments.


Assuntos
Aspartato Aminotransferases/metabolismo , Biomarcadores/metabolismo , Cádmio/toxicidade , Gastrópodes/metabolismo , Hemócitos/metabolismo , Metalotioneína/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Sobrevivência Celular/efeitos dos fármacos , Exposição Ambiental , Gastrópodes/química , Gastrópodes/efeitos dos fármacos , Gastrópodes/genética , Hemócitos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Filogenia , Homologia de Sequência de Aminoácidos , Poluentes Químicos da Água/toxicidade
5.
Cell Biochem Funct ; 37(7): 560-568, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31479167

RESUMO

Annexin A1 (AnxA1) is a protein secreted by phagocytic cells which plays a pivotal role on the resolution of inflammation by enhancing phagocytosis carried out by phagocytes. Which factors and intracellular mechanisms are linked to such actions exerted by AnxA1 are yet to be completely understood. In order to investigate such, BV2 microglial cells were transfected with plasmids aimed at down-modulating AnxA1 expression and also treated with exogenous recombinant rAnxA1; gene and protein expression of proliferated-activated receptor γ (PPARγ) and CD36, STAT6 phosphorylation and phagocytosis of apoptotic neurons were investigated. Down-modulating AnxA1 in BV2 cells impaired gene and protein expression of PPARγ, effects reversed by treatment with recombinant AnxA1 (rAnxA1). Lower levels of CD36 were also verified in AnxA1 down-modulated BV2 cells. AnxA1-mediated phagocytosis of apoptotic cells was abrogated due to blockade of PPARγ activation, and in AnxA1 down-modulated cells exogenous AnxA1 failed to exert any effects on phagocytosis. Lower levels of STAT6/pSTAT6 in AnxA1 down-modulated BV2 cells suggest the involvement of this transcription factor with PPARγ and CD36 synthesis and actions. Data here shown suggest that there is a probable connection between AnxA1, PPARγ, and CD36, which must all act in association in order for efferocytosis to occur properly. AnxA1-mediated phosphorylation of STAT6 is probably involved with intracellular pathways involving PPARγ and CD36 actions. These data evidence that PPARγ/CD36 play a role on AnxA1-mediated efferocytosis in microglial cells. SIGNIFICANCE OF THE STUDY: The findings of this work provide evidence that the glucocorticoid-mediated protein annexin A1 modulates PPARγ expression and that PPARγ is important for annexin A1-mediated efferocytosis. Only recently the interaction between these two factors has begun to be explored, and knowledge on associated cell mechanisms are still scarce. Elucidating how annexin A1 and PPARγ interact with one another provides basis for further research aimed at understanding molecular pathways and cell signaling events involved with these factors, expanding existing knowledge on the anti-inflammatory effects of such factors.


Assuntos
Anexina A1/metabolismo , Microglia/metabolismo , PPAR gama/metabolismo , Fagocitose , Animais , Linhagem Celular , Perfilação da Expressão Gênica , Humanos , Camundongos , Microglia/citologia , PPAR gama/genética , Ratos
6.
J Agric Food Chem ; 67(40): 11230-11235, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31523955

RESUMO

Ochratoxin A (OTA) is a mycotoxin which could cause strong immunosuppressive toxicological effects in animals and humans. Heterophil extracellular traps (HETs) as a novel defense of chicken heterophils play an important role against pathogen infection. It has been reported that OTA can weaken the phagocytosis function of neutrophils. However, whether or not OTA shows immunosuppressive effects on HET release remains unclear. In the present study, we aim to first investigate the effects of OTA on HET release and then try to clarify the mechanisms in this process. OTA-induced HET structures were observed and analyzed by fluorescence confocal microscopy. The quantitative determination of OTA-induced HETs was measured by PicoGreen and a fluorescence microplate. The results clearly showed that OTA obviously induced the release of HET-like structures in heterophils, and these extracellular networks were composed by chromatin decorated with histones and neutrophil elastase. Reactive oxygen species (ROS) production was also increased in the process of OTA-induced HET formation. Furthermore, the inhibitors of NADPH oxidase, ERK [Formula: see text], and p38 MAPK signaling pathways significantly decreased OTA-induced HET formation. The abovementioned results suggest that OTA-induced HET formation is related to ROS production dependent on the activation of NADPH oxidase, ERK [Formula: see text], and p38 MAPK signaling pathways. Taken together, this study first shows that OTA possesses the ability to trigger HET formation, which provides our understanding of the host that continuously suffered OTA exposure leading to the hyporeactivity of the immune system against infection.


Assuntos
Galinhas/imunologia , MAP Quinases Reguladas por Sinal Extracelular/imunologia , Armadilhas Extracelulares/imunologia , NADPH Oxidases/imunologia , Neutrófilos/efeitos dos fármacos , Ocratoxinas/toxicidade , Espécies Reativas de Oxigênio/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Animais , Galinhas/genética , MAP Quinases Reguladas por Sinal Extracelular/genética , Armadilhas Extracelulares/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , NADPH Oxidases/genética , Neutrófilos/enzimologia , Neutrófilos/imunologia , Fagocitose , Proteínas Quinases p38 Ativadas por Mitógeno/genética
7.
Eur J Pharm Biopharm ; 143: 70-79, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446045

RESUMO

Controlled drug delivery to the lungs is promising with plentiful advantages over current rapid release products. However, alveolar macrophage clearance has severely hindered the application of inhaled controlled release preparations. The objective of our study was to explore the feasibility to decorate poly(lactide-co-glycolide) (PLGA) microparticles with endogenous phospholipids found in the deep lungs, thus, to regulate the interplay with alveolar macrophages. The influence of the phospholipid amount and type on macrophage uptake of PLGA microparticles was investigated systemically under both in vitro (RAW264.7 and NR8383) and in vivo conditions. The uptake rate (k) by macrophages, in vivo elimination rate from the bronchoalveolar lavage fluid (k') and elimination rate from the whole lung (k″) were used as parameters for evaluation. Our data showed that a modification with dipalmitoyl phosphatidylcholine (DPPC) enhanced the macrophage phagocytosis significantly over the unmodified counterparts. Thereafter, using the same modification ratio, remarkable enhancement of macrophage uptake was found in the presence of different types of other phospholipids, especially with distearoyl phosphatidylethanolamine (DSPE). When replaced by a poly(ethylene glycol)-conjugated version of DSPE the uptake of the modified PLGA microparticles was reduced by ~200%. Meanwhile, the drug content in the lung tissue was improved by 3-fold (area under the curve value). Finally, it was possible to establish a correlation between in vitro phagocytosis and in vivo lung elimination rate for the investigated formulations. Overall, our study demonstrated that phospholipids play an important role in modulating the clearance of microparticle-based drug delivery vehicles, which gives a meaningful insight into the development of prolonged drug release system for inhalation.


Assuntos
Macrófagos Alveolares/metabolismo , Fosfolipídeos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , 1,2-Dipalmitoilfosfatidilcolina/química , Administração por Inalação , Animais , Linhagem Celular , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Pulmão/metabolismo , Camundongos , Fagocitose/efeitos dos fármacos , Fosfatidilgliceróis/química , Polietilenoglicóis/química , Células RAW 264.7
8.
J Photochem Photobiol B ; 198: 111594, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31446177

RESUMO

Two distinct classes of compounds, (E)-2-(((3-amino-4-nitrophenyl) imino) methyl)-5-(diethylamino) phenol (SB) and 5-(diethylamino)-2-(5-nitro-1H-benzo[d]imidazol-2-yl) phenol (IM) were synthesized. SB, a bright red colored compound was crystallized in acetonitrile as a triclinic crystal system while IM, yellow colored compound crystallized as a monoclinic crystal system in dimethylformamide by vapor diffusion of diethylether. These compounds were characterized using spectroscopic techniques (IR, UV-visible, 1H, and 13C NMR), and X-ray crystallography. SB and IM displayed classical and non-classical H-bonding involving C-H…O and π…π interactions. These compounds detected hypochlorite ions in aqueous DMSO (1: 9, v/v, HEPES buffer, pH 7.4), and detection was visible via color changes by naked eye. We also performed UV-visible and fluorescence titrations, showing detection limits of 8.82 × 10-7 M for SB and 2.44 × 10-7 M for IM. The fluorometric responses from SB and IM were also studied against different ROS and anions. DFT calculations were performed to strengthen the proposed sensing mechanisms of both SB and IM. Hypochlorite, which is endogenously generated by myeloperoxidase in endosomes, was specifically visualized using SB and IM in lipopolysaccharide-treated RAW264.7 cells. These probes were also used to image the generation of hypochlorite by RAW264.7 cells during phagocytosis of non-fluorescent polystyrene beads.


Assuntos
Ácido Hipocloroso/metabolismo , Fenóis/química , Animais , Ânions/química , Teoria da Densidade Funcional , Concentração de Íons de Hidrogênio , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Microscopia Confocal , Fagocitose , Fenóis/síntese química , Poliestirenos/química , Poliestirenos/metabolismo , Células RAW 264.7 , Espectrofotometria
9.
Int J Nanomedicine ; 14: 5229-5242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371958

RESUMO

Purpose: Dexamethasone (Dex) has long been used as a potent immunosuppressive agent in the treatment of inflammatory and autoimmune diseases, despite serious side effects. In the present study, Dex and model antigen ovalbumin (OVA) were encapsulated with poly(lactic-co-glycolic acid) to deliver Dex and OVA preferentially to phagocytic cells, reducing systemic side effects of Dex. The OVA-specific immune tolerance-inducing activity of the nanoparticles (NPs) was examined. Methods: Polymeric NPs containing OVA and Dex (NP[OVA+Dex]) were prepared by the water-in-oil-in-water double emulsion solvent evaporation method. The effects of NP[OVA+Dex] on the maturation and function of immature dendritic cells (DCs) were examined in vitro. Furthermore, the OVA-specific immune tolerizing effects of NP[OVA+Dex] were confirmed in mice that were intravenously injected or orally fed with the NPs. Results: Immature DCs treated in vitro with NP[OVA+Dex] did not mature into immunogenic DCs but instead were converted into tolerogenic DCs. Furthermore, profoundly suppressed generation of OVA-specific cytotoxic T cells and production of OVA-specific IgG were observed in mice injected with NP[OVA+Dex], whereas regulatory T cells were concomitantly increased. Feeding of mice with NP[OVA+Dex] also induced OVA-specific immune tolerance. Conclusion: The present study demonstrates that oral feeding as well as intravenous injection of poly(lactic-co-glycolic acid) NPs encapsulating both antigen and Dex is a useful means of inducing antigen-specific immune tolerance, which is crucial for the treatment of autoimmune diseases.


Assuntos
Antígenos/imunologia , Materiais Biocompatíveis/química , Dexametasona/farmacologia , Epitopos/imunologia , Tolerância Imunológica , Nanopartículas/química , Administração Oral , Animais , Apresentação do Antígeno/efeitos dos fármacos , Citocinas/biossíntese , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Imunidade/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Ovalbumina/imunologia , Fagocitose/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo
10.
Zhonghua Yi Xue Za Zhi ; 99(30): 2355-2361, 2019 Aug 13.
Artigo em Chinês | MEDLINE | ID: mdl-31434416

RESUMO

Objective: To investigate the role of actin-related protein 2-3 complex (Arp2/3) complex on phagocytosis of alveolar macrophages (AMs) in a mouse model of chronic obstructive pulmonary (COPD). Methods: Forty mice were randomly divided into healthy control group, healthy Arp2/3 complex inhibitor (CK666) group, COPD group and COPD CK666 group with 10 mice in each group. COPD group and COPD CK666 group were established by cigarette smoke exposure, and the control group had no smoke exposure. After 90 days of molding, AMs were isolated from lung tissue of mice in each group. Mean fluorescence intensity (MFI) and the positive percent of AMs engulfing fluorescein isothiocyanate-labeled Escherchina coli (FITC-E.coli) (AM%) were detected by flow cytometry. Western blot was applied to detect protein. Laser scanning confocal microscopy was used to measure the mean optical density of Arp2, F-actin and engulfed FITC-E. coli and quantify the colocalization of Arp2 and F-actin by a Manders' overlap coefficient. Scanning electron microscopy was used to observe the ultrastructure of AM phagocytizing FITC-E.coli. Results: Phagocytosis of AM: MFI and AM% in the COPD group were significantly decreased than those in the healthy control group[(4 702±243), (8 684±234) and (32.21±1.66)%, (65.88±1.77)%, all P<0.01]. MFI and AM% in the COPD CK666 group [(3 597±307), (22.09±1.89)%] and in the healthy CK666 group [(7 446±236), (50.09±1.64)%] were decreased compared to those in their respective control groups (all P<0.01). The expressions of protein of Arp2 and F-actin in the COPD group were significantly decreased than those in the healthy control group (0.508±0.025, 0.813±0.040 and 0.462±0.029, 0.720±0.039) (all P<0.01). The F-actin in the COPD CK666 group (0.265±0.014) and in the healthy CK666 group (0.637±0.032) were significantly decreased compared to those in their respective control groups (all P<0.01). The mean optical density of Arp2, F-actin and FITC-E.coli in the COPD group were significantly decreased compared to those in the healthy group (34.43±0.56, 142.83±1.90 and 61.59±0.70, 145.93±3.05 and 41.49±0.33, 189.17±2.60) (all P<0.01); the mean optical density of F-actin, FITC-E. coli in the COPD CK666 group (37.73±1.04, 28.84±2.95) and in the healthy CK666 group (137.07±1.35, 157.46±1.00) were significantly decreased compared to those in their respective control groups (all P<0.01). The Manders' overlap coefficient of Arp2 and phalloidin' coefficient in the COPD group (0.395±0.014) were significantly decreased than the healthy control group (0.395±0.014 and 0.880±0.002, P<0.01). The Manders' overlap coefficient of Arp2 and phalloidin' coefficient in the COPD CK666 group (0.297±0.006) and in the healthy CK666 group (0.737±0.031) were significantly decreased compared to those in their respective control groups (all P<0.01). Shape of AM: Long filopodia protruding and plentiful dorsal ruffle can be seen in AM from the healthy control group; AM pseudopods extension and dorsal ruffle reduced in the health CK666 group; there were pseudopods and dorsal ruffle defects in the COPD group and the COPD CK666 group. Positive correlations existed between the proteins of Arp2, F-actin with MFI. Positive correlations also existed between the Manders' overlap coefficient of Arp2 and phalloidin' coefficient with MFI. Conclusion: Decreased activity of Arp2/3 complex leads to low phagocytosis of AM in COPD mice, and AM in COPD mice is more sensitive to Arp2/3 complex inhibitor.


Assuntos
Macrófagos Alveolares , Doença Pulmonar Obstrutiva Crônica , Complexo 2-3 de Proteínas Relacionadas à Actina , Animais , Escherichia coli , Camundongos , Fagocitose
11.
J Chem Ecol ; 45(8): 715-724, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31385154

RESUMO

Plants emit a specific blend of volatiles in response to herbivory and these volatiles, which often attract predators and parasitoids function as an indirect plant defense. The impact of plant volatiles in shaping herbivore defenses is unclear. Here, we report that specific plant volatiles induce immune responses in the polyphagous herbivore, Spodoptera litura. We characterized the hemocyte profile and established their functional significance with respect to ontogeny and exposure to specific plant volatiles. Fifth instar larvae showed the highest number and hemocytes diversity. We characterized seven different types of hemocytes, of which granulocytes performed phagocytosis, oenocytoids showed melanization activity, and plasmatocytes along with granulocytes and oenocytoids were found to be involved in encapsulation. Among the six volatiles tested, exposure to (E)-ß-ocimene caused the highest increase in total hemocytes number (THC) followed by linalool and (Z)-3-hexenyl acetate exposure. Although THC did not differ between these three volatile treatments, circulating hemocytes diversity varied significantly. (E)-ß-ocimene exposure showed higher number of plasmatocytes and phenol oxidase activity. The interaction of the parasitic wasp Bracon brevicornis with (E)-ß-ocimene exposed larvae was poor in terms of delayed paralysis and lower egg deposition. In choice assays, the wasp showed clear preference towards control larvae indicating (E)-ß-ocimene treatment renders the host unattractive. Hemocyte profiles post-parasitoid exposure and (E)-ß-ocimene treatment were similar indicating cue-based priming. When challenged with Bacillus thuringiensis, linalool exposure resulted in the highest survival as compared to other volatiles. Our results show that specific HIPVs can modulate cellular immunity of S. litura, revealing a new role for HIPVs in tri-trophic interactions.


Assuntos
Compostos Orgânicos Voláteis/farmacologia , Vespas/fisiologia , Alcenos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Hemócitos/citologia , Hemócitos/efeitos dos fármacos , Hemócitos/metabolismo , Herbivoria , Interações Hospedeiro-Parasita , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Larva/fisiologia , Monofenol Mono-Oxigenase/metabolismo , Monoterpenos/farmacologia , Oviposição/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Plantas/química , Plantas/metabolismo , Plantas/parasitologia , Compostos Orgânicos Voláteis/química , Vespas/imunologia
12.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(7): 913-915, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31441422

RESUMO

OBJECTIVE: As one of the top three causes of death in the world, chronic obstructive pulmonary disease (COPD)is a serious hazard to human health. Macrophages play an important role in COPD, and their efferocytosis function is essential for ending chronic inflammation of COPD. Efferocytosis damage of alveolar macrophages (AM) in patients with COPD causes the rising of bacterial infection and airway bacterial colonization risk in lungs, which is the main reason for the acute exacerbation and the rising of incidence rate and mortality rate in COPD. In recent years, the regulation of macrophage efferocytosis function in COPD has becoming a research hotspot. Progress on the role of macrophage efferocytosis function on COPD, and the breakthrough points of improving AM efferocytosis dysfunction by traditional Chinese medicine is reviewed, so as to provide new ideas for the prevention and treatment of COPD.


Assuntos
Macrófagos Alveolares , Doença Pulmonar Obstrutiva Crônica , Líquido da Lavagem Broncoalveolar , Sepultamento , Humanos , Fagocitose
13.
Anticancer Res ; 39(8): 4503-4509, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366552

RESUMO

BACKGROUND/AIM: Oral administration of Pantoea agglomerans-derived lipopolysaccharide (LPSp) has been reported to have a preventive effect against various lifestyle-related diseases. Therefore, we examined the preventive effect on high blood pressure, which is a kind of reserve arm for lifestyle-related diseases. MATERIALS AND METHODS: Spontaneous hypertensive rat (SHR) and WKY rat were bred from 6 to 16 weeks of age. SHR were orally administered 100 µg/kg LPSp and 0.1% NaCl, and blood pressure was measured at 6, 10, 13 and 16 weeks. Furthermore, at 16 weeks of age, blood biochemical markers were measured and microbial community composition was analyzed. RESULTS: SHRs developed hypertension with age, which was exacerbated by salt loading. Although there was almost no reduction in blood pressure in SHRs that received LPSp. It was suppressed at 13-16 weeks of age in those with salt loading. CONCLUSION: Oral administration of LPSp showed a preventive effect on salt-loaded hypertension.


Assuntos
Citocinas/genética , Hipertensão/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Pantoea/química , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Hipertensão/genética , Hipertensão/patologia , Lipopolissacarídeos/química , Masculino , Fagocitose/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Sais/toxicidade
14.
Anticancer Res ; 39(8): 4533-4537, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366556

RESUMO

BACKGROUND/AIM: Serum-derived macrophage activating factor, serum-MAF, is known to increase the phagocytic activity of macrophages by enhancing the engulfment efficiency. To elucidate the mechanisms underlying phagocytic activation, morphological changes were observed and analyzed. MATERIALS AND METHODS: Morphological changes in macrophages were observed and quantitatively analyzed using scanning electron microscope (SEM) and confocal microscope. RESULTS: SEM and confocal microscopy images revealed frill-like structures and active actin accumulations, respectively, in serum-MAF treated macrophages. Actin accumulation was induced within 5 min following serum-MAF treatment. CONCLUSION: Serum-MAF induced a rapid rearrangement of cytoskeletal actin and enhanced phagocytic activity. Findings of the current study may contribute to the development of techniques that facilitate activation of the human immune system, which in turn may be beneficial for cancer immunotherapy.


Assuntos
Actinas/química , Macrófagos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-maf/farmacologia , Actinas/ultraestrutura , Humanos , Imunoterapia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Microscopia Confocal , Microscopia Eletrônica de Varredura , Proteínas Proto-Oncogênicas c-maf/genética , Células U937 , Proteína de Ligação a Vitamina D/química , Proteína de Ligação a Vitamina D/metabolismo
15.
J Anim Sci ; 97(8): 3326-3336, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31299068

RESUMO

Hypocalcemia in dairy cows is often associated with inflammation-related disorders such as metritis and mastitis. The protein encoded by the Ca2+ release-activated calcium modulator 1 (ORAI1) gene is a membrane Ca2+ channel subunit that is activated when Ca2+ stores are depleted. Polymorphonuclear neutrophils (PMNL) have a crucial role in the defense against infection through migration, adhesion, chemotaxis, phagocytosis, and reactive oxygen species (ROS) production in response to pathogens. Whether hypocalcemia affects the activity of PMNL and if ORAI1 is involved remains unknown. To address this, PMNL were isolated at 3 d of calving from dairy cows diagnosed as clinically healthy (n = 20, CONTROL) or with plasma concentration of calcium < 2.0 mmol/L as a criterion for diagnosis of subclinical hypocalcemia (n = 20, HYPOCAL). PMNL isolated from both groups of cows were treated with or without the sarcoendoplasmic Ca2+ ATPase inhibitor thapsigargin, Ca2+ ionophore Ionomycin, and ORAI1 blocker 2APB. The intracellular Ca2+ concentration, ORAI1 abundance, ROS, phagocytosis rate, migration, and adhering capacity of treated PMNL were evaluated. Some of the in vitro assays also included use of small interfering ORAI1 RNA (siORAI1), 100 nM 1,25(OH)2D3, or 100 nM parathyroid hormone (PTH). Intracellular Ca2+ concentration was markedly lower in HYPOCAL. In addition, ORAI1 was detected in PMNL plasma membrane via FACS and was markedly lower in cows with HYPOCAL. Migration, adhesion capacity, and phagocytosis rate of PMNL were lower in response to HYPOCAL. Furthermore, plasma and PMNL concentration of nucleosome assembly protein (NAP2) and pro-platelet basic protein (CXCL7) was markedly lower with HYPOCAL. All these changes were associated with lower ROS production by PMNL. Thapsigargin and ionomycin treatment in vitro increased ORAI1 expression, migration of PMNL, adhering capacity, phagocytosis rate, and ROS production; conversely, those effects were abrogated by siORAI1 and ORAI1 inhibitor 2APB treatment. Also cytosolic Ca2+ concentration and ORAI1 abundance were increased by 1,25(OH)2D3 and PTH supplementation. Overall, the data indicate that failure of PMNL to uptake Ca2+ due to downregulation of ORAI1 during subclinical hypocalcemia is a factor contributing to impaired PMNL function. In addition, plasma PTH or 1,25(OH)2D3 could regulate ORAI1 and also participate in the regulation of PMNL activity.


Assuntos
Cálcio/metabolismo , Bovinos/genética , Regulação da Expressão Gênica , Hipocalcemia/veterinária , Proteína ORAI1/metabolismo , Animais , Bovinos/imunologia , Bovinos/fisiologia , Indústria de Laticínios , Feminino , Hipocalcemia/imunologia , Inflamação/veterinária , Neutrófilos/imunologia , Proteína ORAI1/genética , Hormônio Paratireóideo/metabolismo , Fagocitose , Período Pós-Parto , RNA Interferente Pequeno , Espécies Reativas de Oxigênio/metabolismo
16.
Res Vet Sci ; 125: 333-344, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31352282

RESUMO

Minthostachys verticillata essential oil (EO) is a natural product that reports immunomodulatory effects on human T cells as well as anti-inflammatory activity. Bovine mastitis is a worldwide disease, mainly caused by bacteria, affecting milk quality and yield, leading to high economic losses. Environmental pathogens, as Enterococcus faecium, are implicated in the disease. Antibiotic therapy is adequate, although it can leave residues in milk, causing problems in human health. The search of immunomodulatory substances for bovine mastitis treatment is a promising alternative strategy. The aim of this study was to characterize the effect of M. verticillata EO on macrophage phagocytosis and evaluate its immunomodulatory and protective effects in mice challenged with E. faecium. The results showed that EO activated macrophage phagocytosis mechanisms inducing reactive oxygen species production. Moreover, EO modulated the innate immune response in mammary glands of female Balb/c mice challenged with E. faecium decreasing the infiltration of polymorphonuclear neutrophils and IL-1ß and TNF-α mRNA expression. In addition, EO increased the expression of IL-10 in the last hours of infection. Treatment with EO did not increase the number of activated CD4+ or CD8+ T cells or the production of specific antibodies. These results suggest that EO play an important role in helping to resolve the infection in the first hours without activating adaptive immunity. In addition, a marked decrease of the bacterial count in the glands of mice treated with EO was observed. A natural product such as M. verticillata EO could have a potential use to control bovine mastitis.


Assuntos
Enterococcus faecium/fisiologia , Imunidade Inata/efeitos dos fármacos , Lamiaceae/química , Macrófagos/efeitos dos fármacos , Mastite Bovina/tratamento farmacológico , Óleos Voláteis/farmacologia , Fagocitose/efeitos dos fármacos , Animais , Bovinos , Feminino , Fatores Imunológicos/farmacologia , Macrófagos/imunologia , Mastite Bovina/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Óleos Voláteis/química , Substâncias Protetoras/farmacologia
17.
Vox Sang ; 114(6): 576-587, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31281973

RESUMO

BACKGROUND AND OBJECTIVES: The accumulation of microvesicles in erythrocyte concentrates during storage or irradiation may be responsible for clinical symptoms such as inflammation, coagulation and immunization. Our aim was to determine whether any of the cluster of differentiation (CD) molecules responsible for important functions are present on microvesicles, and if their expression level is dependent on the storage period of erythrocyte concentrates. MATERIAL AND METHODS: Erythrocyte microvesicles were isolated from 'fresh' (2nd day) and 'old' (42nd day) stored erythrocyte concentrates. Qualitative cytometric analysis of 0·5 µm, erythrocyte-derived, PS-exposing vesicles was performed using the annexin V-FITC, anti-CD235a-PE antibody and calibrated beads. The microvesicles were also visualized under a confocal microscope. The expression of the molecules CD235a, CD44, CD47, CD55, CD59 and of phosphatidylserine (PS) was compared using flow cytometry. Measurements of microvesicle phagocytosis by human monocytes were carried out using a flow cytometer and a confocal microscope. RESULTS: The analysis of the microvesicles with calibration beads allowed us to identify these structures with a diameter of about 0·5 µm in the 'fresh' and 'old' samples. At day 2, the microvesicles had elevated expression levels of CD47, reduced expression levels of PS, CD55 and CD59. The phagocytosis index was higher for the microvesicles isolated from the 42-day-old erythrocyte concentrates. CONCLUSION: This research may bring us closer to understanding the factors responsible for erythrocyte ageing and to evaluate the quality of stored red blood concentrates intended for transfusion.


Assuntos
Transfusão de Sangue , Eritrócitos/fisiologia , Vesículas Extracelulares/fisiologia , Glicoproteínas de Membrana/fisiologia , Monócitos/fisiologia , Fagocitose , Antígeno CD47/análise , Antígeno CD47/genética , Antígenos CD55/análise , Antígenos CD55/genética , Antígenos CD59/análise , Antígenos CD59/genética , Eritrócitos/citologia , Eritrócitos/metabolismo , Citometria de Fluxo , Expressão Gênica , Humanos , Receptores de Hialuronatos/análise , Receptores de Hialuronatos/genética , Fosfatidilserinas/análise
18.
Carbohydr Polym ; 222: 114993, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320068

RESUMO

ß-glucans trigger the proinflammatory responses of innate immune cells to enhance the host defense. A variety of ß-glucans were identified as strong immune stimulator and exerted antitumor activities. Our previous work indicates that a ß-1,3/1,6-glucan (BG136) derived from marina alga Durvillaea antarctica promotes the proinflammatory responses in macrophage cell line RAW264.7. In the present study, we further explored its antitumor effects in vivo as an immune stimulator. The data shows that BG136 alone decreases the tumor burdens in DLD1 xenograft and AOM-DSS induced tumor models. BG136 also augments the antitumor effects of PD-1 antibody in B16 syngeneic tumor model. BG136 increases macrophage phagocytosis, enhances cytokine/chemokine secretion and modulates the systemic and intratumoral immune cell composition. Collectively, these data suggest that BG136 might act as an immune stimulator to exert antitumor effects in vivo.


Assuntos
Adjuvantes Imunológicos/farmacologia , Glucanos/farmacologia , Neoplasias/imunologia , Animais , Linhagem Celular Tumoral , Citocinas/imunologia , Humanos , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Feófitas/metabolismo , Fagocitose/efeitos dos fármacos , Receptor de Morte Celular Programada 1/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
19.
Environ Pollut ; 252(Pt B): 1764-1771, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295695

RESUMO

Phagocytosis suppression induced by nanoparticles (NPs) exposure is increasingly reported in marine species. However, the mechanisms underlying this impact remain poorly understood. In order to improve our present understanding of the immunotoxicity of NPs, acute (96 h) TiO2 NP exposure and rescue trials via exogenous supply of Ca2+ were performed in the blood clam, Tegillarca granosa. The results show that the phagocytosis rate, cell viability, and intracellular Ca2+ concentration of haemocytes were significantly suppressed, whereas the intracellular ROS concentration of haemocytes significantly increased upon nTiO2 exposure. Exposure to nTiO2 also led to the significant downregulation of Caspase-3, Caspase-6, apoptosis regulator Bcl-2, Bcl-2-associated X, calmodulin kinase II, and calmodulin kinase kinase II. Furthermore, the toxic impacts of nTiO2 were partially mitigated by the addition of exogenous Ca2+, as indicated by the recovery tendency in almost all the measured parameters. The present study indicates that Ca2+ signaling could be one of the key pathways through which nTiO2 attacks phagocytosis.


Assuntos
Apoptose/efeitos dos fármacos , Arcidae/efeitos dos fármacos , Cálcio/farmacologia , Hemócitos/efeitos dos fármacos , Nanopartículas/toxicidade , Fagocitose/efeitos dos fármacos , Titânio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Apoptose/genética , Arcidae/fisiologia , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Hemócitos/patologia
20.
Fish Shellfish Immunol ; 92: 813-820, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271840

RESUMO

B cells have been found to have phagocytic activity in recent years, but the studies exploring the regulation mechanisms are still lacking to date. In the present study, the recombinant interleukin-10 (rIL-10) was obtained to study the function of IL-10 on phagocytosis of flounder (Paralichthys olivaceus) mIgM+ B lymphocytes. Flow cytometric analysis showed that IL-10 significantly enhanced the phagocytosis of Edwardsiella tarda but not Lactococcus lactis by mIgM+ B lymphocytes. Moreover, significantly higher intracellular ROS levels were detected in mIgM+ B lymphocytes following rIL-10 stimulation. The qRT-PCR analysis showed that rIL-10 could upregulate the expressions of IL-10Rb and Stat3 in mIgM+ B lymphocytes, suggesting that IL-10 might modulate the phagocytosis of mIgM+ B lymphocytes by activating IL-10R and Stat3. In addition, we also found that the enhancing effect of IL-10 on phagocytosis and intracellular ROS levels of mIgM+ B lymphocytes were suppressed by the administration of niclosamide. These results collectively demonstrated that IL-10 enhanced mIgM+ B lymphocyte-mediated phagocytosis of E. tarda and intracellular bactericidal ability, and IL-10R and Stat3 might play a curial role in the regulation of IL-10-stimulated phagocytosis, which would deepen our understanding of regulation mechanism of B cell phagocytosis.


Assuntos
Linfócitos B/imunologia , Proteínas de Peixes/imunologia , Linguados/imunologia , Interleucina-10/imunologia , Fagocitose/imunologia , Animais , Edwardsiella tarda/fisiologia , Lactococcus lactis/fisiologia , Proteínas Recombinantes/imunologia
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