Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 767
Filtrar
1.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414755

RESUMO

BACKGROUND: The instructions of manufacturers of methodologies for anti-HIV-1/2 antibodies screening tests re-commend avoiding analyzing blood samples with hemolysis or lipemia, but they do not mention references about scientific studies evaluating their interference. The increased need for an opportune detection of HIV infection to avoid its spread has led to public health institutions including routine HIV screening even in internal medicine and emergency rooms. Nevertheless, these blood samples are usually associated with the presence of lipemia and/ or hemolysis, leaving doubt for probable misinterpretations. This fact highlights the need for applying verification techniques, established under the internal methodological conditions of each laboratory, in order to increase the coverage of HIV screening and to ensure the reliability of their results. METHODS: Following the ethics committee approval and patient's informed consent, a confirmed anti-HIV-1 positive human serum (undetectable viral load and p24 antigen, and stable total lymphocytes > 30%) was obtained. This work describes techniques for the semiquantitative analysis of anti-HIV antibodies of three commercial HIV-screening methodologies (immunochromatography, enzyme-immunoassay and chemiluminescence) and to deter-mine the detection limit of these screening tests, as well as evaluating the maximum concentration of total lipids and of free hemoglobin that do not interfere in the detection limits. RESULTS: The highest analyzed concentration of total lipid (870 mg/dL) did not interfere with the detection limits of anti-HIV-1 antibodies in any of the evaluated methodologies. Free hemoglobin presented interference at different concentrations depending on the methodology: immunochromatography (0.57 g/dL)), enzyme-immunoassay (8.6 g/dL), and chemiluminescence (11.5 g/dL)). CONCLUSIONS: Concentrations of lipemia above postprandial levels or hemolysis induced by experimental manipulation might not interfere with HIV-serological screening. Determining the maximum permissible limits of lipemia and hemolysis by each manufacturer or laboratory based on an internal evaluation of their serological methodology would increase the reliability of HIV-diagnosis in internal medicine and emergency rooms and in patients with dyslipidemia or physiological hemolysis.


Assuntos
Anticorpos Anti-HIV/imunologia , Infecções por HIV/diagnóstico , Soropositividade para HIV/diagnóstico , HIV-1/imunologia , Sorodiagnóstico da AIDS/métodos , Anticorpos Anti-HIV/sangue , Infecções por HIV/sangue , Infecções por HIV/virologia , Soropositividade para HIV/sangue , Soropositividade para HIV/virologia , HIV-1/fisiologia , Hemoglobinas/imunologia , Hemoglobinas/metabolismo , Hemólise/imunologia , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/imunologia , Limite de Detecção , Lipídeos/sangue , Lipídeos/imunologia , Sensibilidade e Especificidade
2.
Nutrients ; 11(7)2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31262028

RESUMO

Raw cow's milk was previously shown to suppress allergic symptoms in a murine model for food allergy. In the present study, we investigated the contribution of fat content and heat-sensitive milk components to this allergy-protective effect. In addition, we determined the potency of alkaline phosphatase (ALP), a heat-sensitive raw milk component, to affect the allergic response. C3H/HeOuJ mice were treated with raw milk, pasteurized milk, skimmed raw milk, pasteurized milk spiked with ALP, or phosphate-buffered saline for eight days prior to sensitization and challenge with ovalbumin (OVA). Effects of these milk types on the allergic response were subsequently assessed. Similar to raw milk, skimmed raw milk suppressed food allergic symptoms, demonstrated by a reduced acute allergic skin response and low levels of OVA-specific IgE and Th2-related cytokines. This protective effect was accompanied by an induction of CD103+CD11b+ dendritic cells and TGF-ß-producing regulatory T cells in the mesenteric lymph nodes. Pasteurized milk was not protective but adding ALP restored the allergy-protective effect. Not the fat content, but the heat-sensitive components are responsible for the allergy-protective effects of raw cow's milk. Adding ALP to heat-treated milk might be an interesting alternative to raw cow's milk consumption, as spiking pasteurized milk with ALP restored the protective effects.


Assuntos
Fosfatase Alcalina/imunologia , Dermatite Atópica/prevenção & controle , Manipulação de Alimentos/métodos , Hipersensibilidade Alimentar/prevenção & controle , Proteínas do Leite/imunologia , Pasteurização , Animais , Basófilos/imunologia , Basófilos/metabolismo , Células Cultivadas , Citocinas/metabolismo , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Imunoglobulinas/sangue , Lipídeos/imunologia , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos Endogâmicos C3H , Ovalbumina , Desnaturação Proteica , Pele/imunologia , Pele/metabolismo , Baço/imunologia , Baço/metabolismo
3.
Blood ; 134(17): 1458-1468, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31300403

RESUMO

Deep vein thrombosis (DVT) is a common cardiovascular disease with a major effect on quality of life, and safe and effective therapeutic measures to efficiently reduce existent thrombus burden are scarce. Using a comprehensive targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics approach, we established temporal clusters of endogenously biosynthesized specialized proresolving mediators (SPMs) and proinflammatory and prothrombotic lipid mediators during DVT progression in mice. Administration of resolvin D4 (RvD4), an SPM that was enriched at the natural onset of thrombus resolution, significantly reduced thrombus burden, with significantly less neutrophil infiltration and more proresolving monocytes in the thrombus, as well as an increased number of cells in an early apoptosis state. Moreover, RvD4 promoted the biosynthesis of other D-series resolvins involved in facilitating resolution of inflammation. Neutrophils from RvD4-treated mice were less susceptible to an ionomycin-induced release of neutrophil extracellular traps (NETs), a meshwork of decondensed chromatin lined with histones and neutrophil proteins critical for DVT development. These results suggest that delivery of SPMs, specifically RvD4, modulates the severity of thrombo-inflammatory disease in vivo and improves thrombus resolution.


Assuntos
Ácidos Graxos Insaturados/uso terapêutico , Trombose Venosa/tratamento farmacológico , Animais , Progressão da Doença , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Mediadores da Inflamação/imunologia , Lipídeos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos/efeitos dos fármacos , Trombose Venosa/imunologia , Trombose Venosa/patologia
4.
Chem Asian J ; 14(12): 2116-2121, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31042017

RESUMO

The tumor-associated antigen mucin 1 (MUC1) has been pursued as an attractive target for cancer immunotherapy, but the poor immunogenicity of the endogenous antigen hinders the development of vaccines capable of inducing effective anti-MUC1 immunodominant responses. Herein, we prepared synthetic anti-MUC1 vaccines in which the hydrophilic MUC1 antigen was N-terminally conjugated to one or two palmitoyl lipid chains (to form amphiphilic Pam-MUC1 or Pam2 -MUC1). These amphiphilic lipid-tailed MUC1 antigens were self-assembled into liposomes containing the NKT cell agonist αGalCer as an adjuvant. The lipid-conjugated antigens reshaped the physical and morphological properties of liposomal vaccines. Promising results showed that the anti-MUC1 IgG antibody titers induced by the Pam2 -MUC1 vaccine were more than 30- and 190-fold higher than those induced by the Pam-MUC1 vaccine and the MUC1 vaccine without lipid tails, respectively. Similarly, vaccines with the TLR1/2 agonist Pam3 CSK4 as an adjuvant also induced conjugated lipid-dependent immunological responses. Moreover, vaccines with the αGalCer adjuvant induced significantly higher titers of IgG antibodies than vaccines with the Pam3 CSK4 adjuvant. Therefore, the non-covalent assembly of the amphiphilic lipo-MUC1 antigen and the NKT cell agonist αGalCer as a glycolipid adjuvant represent a synthetically simple but immunologically effective approach for the development of anti-MUC1 cancer vaccines.


Assuntos
Vacinas Anticâncer/química , Vacinas Anticâncer/imunologia , Epitopos Imunodominantes/imunologia , Lipídeos/imunologia , Mucina-1/imunologia , Humanos , Lipossomos , Células MCF-7 , Tensoativos
5.
Arch Virol ; 164(7): 1793-1803, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079211

RESUMO

Numerous studies have shown that immunostimulatory complexes containing Quil-A saponin and various antigens are effective in stimulating the immune response and can be used as vaccine preparations for animals and humans. However, Quil-A saponin possesses toxicity and haemolytic activity. In the present work, a saponin-containing preparation named "Glabilox" was isolated from the roots of a Glycyrrhiza glabra L. plant by high-performance liquid chromatography (HPLC). The results showed that Glabilox has no toxicity or haemolytic activity and can form stable immunostimulatory complexes. Subcutaneous immunization of mice with an immunostimulating complex containing Glabilox and H7N1 influenza virus antigens stimulated high levels of humoral and cellular immunity. Vaccination of chickens with the same immunostimulating complex protected 100% of the animals after experimental infection with a homologous virus. Comparative studies showed that the immunogenic and protective activity of immunostimulatory complexes containing Quil-A and immunostimulatory complexes containing Glabilox are comparable to each other. The results of these studies indicated that Glycyrrhiza glabra saponins show great promise as safe and effective adjuvants.


Assuntos
Adjuvantes Imunológicos/farmacologia , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Glycyrrhiza/imunologia , Vírus da Influenza A Subtipo H7N1/imunologia , Influenza Aviária/prevenção & controle , Animais , Linhagem Celular , Embrião de Galinha , Galinhas , Cães , Glicoproteínas/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Influenza Aviária/imunologia , Lipídeos/imunologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Raízes de Plantas/imunologia , Saponinas de Quilaia/imunologia , Saponinas/imunologia , Vacinação
6.
Int J Mol Sci ; 20(10)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100828

RESUMO

In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the complex interaction of immune effector cells, as well as the role of the bone marrow microenvironment in the development, maintenance and progression of AML. Lipids, and in particular omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) have been shown to play a vital role as signaling molecules of immune processes in numerous benign and malignant conditions. While the majority of research in cancer has been focused on the role of lipid mediators in solid tumors, some data are showing their involvement also in hematologic malignancies. There is a considerable amount of evidence that AML cells are targetable by innate and adaptive immune mechanisms, paving the way for immune therapy approaches in AML. In this article we review the current data showing the lipid mediator and lipidome patterns in AML and their potential links to immune mechanisms.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Lipídeos/uso terapêutico , Imunidade Adaptativa/efeitos dos fármacos , Medula Óssea , Progressão da Doença , Ácidos Graxos Ômega-3/imunologia , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-6/imunologia , Ácidos Graxos Ômega-6/uso terapêutico , Ácidos Graxos Insaturados , Neoplasias Hematológicas/tratamento farmacológico , Hematopoese , Humanos , Imunidade Inata/efeitos dos fármacos , Imunoterapia , Inflamação , Leucemia Mieloide Aguda/imunologia , Lipídeos/imunologia , Neoplasias/tratamento farmacológico , Prognóstico , Microambiente Tumoral
7.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(8): 1157-1167, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31051284

RESUMO

BACKGROUND: Natural killer T (NKT) cells in adipose tissue (AT) contribute to whole body energy homeostasis. RESULTS: Inhibition of the glucosylceramide synthesis in adipocytes impairs iNKT cell activity. CONCLUSION: Glucosylceramide biosynthesis pathway is important for endogenous lipid antigen activation of iNKT cells in adipocytes. SIGNIFICANCE: Unraveling adipocyte-iNKT cell communication may help to fight obesity-induced AT dysfunction. Overproduction and/or accumulation of ceramide and ceramide metabolites, including glucosylceramides, can lead to insulin resistance. However, glucosylceramides also fulfill important physiological functions. They are presented by antigen presenting cells (APC) as endogenous lipid antigens via CD1d to activate a unique lymphocyte subspecies, the CD1d-restricted invariant (i) natural killer T (NKT) cells. Recently, adipocytes have emerged as lipid APC that can activate adipose tissue-resident iNKT cells and thereby contribute to whole body energy homeostasis. Here we investigate the role of the glucosylceramide biosynthesis pathway in the activation of iNKT cells by adipocytes. UDP-glucose ceramide glucosyltransferase (Ugcg), the first rate limiting step in the glucosylceramide biosynthesis pathway, was inhibited via chemical compounds and shRNA knockdown in vivo and in vitro. ß-1,4-Galactosyltransferase (B4Galt) 5 and 6, enzymes that convert glucosylceramides into potentially inactive lactosylceramides, were subjected to shRNA knock down. Subsequently, (pre)adipocyte cell lines were tested in co-culture experiments with iNKT cells (IFNγ and IL4 secretion). Inhibition of Ugcg activity shows that it regulates presentation of a considerable fraction of lipid self-antigens in adipocytes. Furthermore, reduced expression levels of either B4Galt5 or -6, indicate that B4Galt5 is dominant in the production of cellular lactosylceramides, but that inhibition of either enzyme results in increased iNKT cell activation. Additionally, in vivo inhibition of Ugcg by the aminosugar AMP-DNM results in decreased iNKT cell effector function in adipose tissue. Inhibition of endogenous glucosylceramide production results in decreased iNKT cells activity and cytokine production, underscoring the role of this biosynthetic pathway in lipid self-antigen presentation by adipocytes.


Assuntos
Adipócitos/metabolismo , Glucosilceramidas/biossíntese , Células T Matadoras Naturais/metabolismo , Adipócitos/citologia , Apresentação do Antígeno , Comunicação Celular , Linhagem Celular , Técnicas de Cocultura , Citocinas/metabolismo , Glucosilceramidas/metabolismo , Humanos , Resistência à Insulina , Lipídeos/imunologia , Ativação Linfocitária , Células T Matadoras Naturais/citologia
8.
Nat Immunol ; 20(5): 626-636, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30936495

RESUMO

Muscle damage elicits a sterile immune response that facilitates complete regeneration. Here, we used mass spectrometry-based lipidomics to map the mediator lipidome during the transition from inflammation to resolution and regeneration in skeletal muscle injury. We observed temporal regulation of glycerophospholipids and production of pro-inflammatory lipid mediators (for example, leukotrienes and prostaglandins) and specialized pro-resolving lipid mediators (for example, resolvins and lipoxins) that were modulated by ibuprofen. These time-dependent profiles were recapitulated in sorted neutrophils and Ly6Chi and Ly6Clo muscle-infiltrating macrophages, with a distinct pro-resolving signature observed in Ly6Clo macrophages. RNA sequencing of macrophages stimulated with resolvin D2 showed similarities to transcriptional changes found during the temporal transition from Ly6Chi macrophage to Ly6Clo macrophage. In vivo, resolvin D2 increased Ly6Clo macrophages and functional improvement of the regenerating muscle. These results reveal dynamic lipid mediator signatures of innate immune cells and provide a proof of concept for their exploitable effector roles in muscle regeneration.


Assuntos
Mediadores da Inflamação/imunologia , Lipídeos/imunologia , Macrófagos/imunologia , Músculo Esquelético/imunologia , Regeneração/imunologia , Animais , Ácidos Docosa-Hexaenoicos/imunologia , Ácidos Docosa-Hexaenoicos/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Perfilação da Expressão Gênica , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Metabolismo dos Lipídeos/imunologia , Lipídeos/análise , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/lesões , Músculo Esquelético/fisiopatologia , Regeneração/genética
9.
Immunol Rev ; 289(1): 173-185, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30977198

RESUMO

The signaling lipid sphingosine 1-phosphate (S1P) plays key roles in many physiological processes. In the immune system, S1P's best-described function is to draw cells out of tissues into circulation. Here, we will review models of S1P distribution in the thymus, lymph nodes, spleen, and nonlymphoid tissues. These models have been challenging to construct, because of the lack of tools to map lipid gradients. Nonetheless, evidence to date suggests that S1P distribution is exquisitely tightly controlled, and that concentrations of signaling-available S1P cannot be predicted by standard rules of thumb. The fine regulation of S1P gradients may explain how S1P can simultaneously direct multiple cell movements both between tissues and circulation and within tissues. It may also make it feasible to develop drugs that enable spatially specific modulation of S1P signaling.


Assuntos
Imunidade Celular , Liases/metabolismo , Lisofosfolipídeos/metabolismo , Esfingosina/análogos & derivados , Animais , Circulação Sanguínea , Movimento Celular , Humanos , Imunomodulação , Lipídeos/imunologia , Transdução de Sinais , Esfingosina/metabolismo
10.
Tuberculosis (Edinb) ; 115: 96-107, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30948183

RESUMO

All mycobacteria, including nontuberculous mycobacteria (NTM), synthesize an array of lipids including phosphatidylinositol mannosides (PIM), lipomannan (LM), and lipoarabinomannan (LAM). While absent from Mycobacterium tuberculosis (M. tb), glycopeptidolipids (GPL) are critical to the biology of NTM. M. tb and some NTM also synthesize trehalose-containing glycolipids and phenolic glycolipids (PGL), key membrane constituents with essential roles in metabolism. While lipids facilitate immune evasion, they also induce host immunity against tuberculosis. However, much less is known about the significance of NTM-derived PIM, LM, LAM, GPL, trehalose-containing glycolipids, and PGL as virulence factors, warranting further investigation. While culling the scientific literature on NTM lipids, it's evident that such studies were relatively few in number with the overwhelming majority of prior work dedicated to understanding lipids from the saprophyte Mycobacterium smegmatis. The identification and functional analysis of immune reactive NTM-derived lipids remain challenging, but such work is likely to yield a greater understanding of the pathogenesis of NTM lung disease. In this review, we juxtapose the vast literature of what is currently known regarding M. tb lipids to the lesser number of studies for comparable NTM lipids. But because GPL is the most widely recognized NTM lipid, we highlight its role in disease pathogenesis.


Assuntos
Lipídeos/biossíntese , Mycobacterium tuberculosis/metabolismo , Bacillus/metabolismo , Parede Celular/imunologia , Parede Celular/fisiologia , Imunidade Celular/fisiologia , Lipídeos/química , Lipídeos/imunologia , Mycobacterium tuberculosis/imunologia , Micobactérias não Tuberculosas/imunologia , Micobactérias não Tuberculosas/metabolismo
11.
Front Immunol ; 10: 122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30837983

RESUMO

Molecular allergology research has provided valuable information on the structure and function of single allergenic molecules. There are several allergens in food and inhalant allergen sources that are able to interact with lipid ligands via different structural features: hydrophobic pockets, hydrophobic cavities, or specialized domains. For only a few of these allergens information on their associated ligands is already available. Several of the allergens are clinically relevant, so that it is highly probable that the individual structural features with which they interact with lipids have a direct effect on their allergenic potential, and thus on allergy development. There is some evidence for a protective effect of lipids delaying the enzymatic digestion of the peanut (Arachis hypogaea) allergen Ara h 8 (hydrophobic pocket), probably allowing this molecule to get to the intestinal immune system intact (sensitization). Oleosins from different food allergen sources are part of lipid storage organelles and potential marker allergens for the severity of the allergic reaction. House dust mite (HDM), is more often associated with allergic asthma than other sources of inhalant allergens. In particular, lipid-associated allergens from Dermatophagoides pteronyssinus which are Der p 2, Der p 5, Der p 7, Der p 13, Der p 14, and Der p 21 have been reported to be associated with severe allergic reactions and respiratory symptoms such as asthma. The exact mechanism of interaction of these allergens with lipids still has to be elucidated. Apart from single allergens glycolipids have been shown to directly induce allergic inflammation. Several-in parts conflicting-data exist on the lipid (and allergen) and toll-like receptor interactions. For only few single allergens mechanistic studies were performed on their interaction with the air-liquid interface of the lungs, in particular with the surfactant components SP-A and SP-D. The increasing knowledge on protein-lipid-interaction for lipophilic and hydrophobic food and inhalant allergens on the basis of their particular structure, of their capacity to be integral part of membranes (like the oleosins), and their ability to interact with membranes, surfactant components, and transport lipids (like the lipid transfer proteins) are essential to eventually clarify allergy and asthma development.


Assuntos
Alérgenos/metabolismo , Antígenos de Plantas/metabolismo , Asma/imunologia , Proteínas de Transporte/metabolismo , Hipersensibilidade/imunologia , Lipídeos/imunologia , Proteínas de Plantas/metabolismo , Alérgenos/imunologia , Animais , Antígenos de Plantas/imunologia , Proteínas de Transporte/imunologia , Humanos , Metabolismo dos Lipídeos , Proteínas de Plantas/imunologia , Plantas , Proteína A Associada a Surfactante Pulmonar/imunologia , Proteína A Associada a Surfactante Pulmonar/metabolismo , Proteína D Associada a Surfactante Pulmonar/imunologia , Proteína D Associada a Surfactante Pulmonar/metabolismo
12.
Mucosal Immunol ; 12(3): 805-815, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30778118

RESUMO

Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is the leading killer due to an infectious organism. Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine approved against TB, however, its efficacy against pulmonary TB is poor. While BCG is currently inoculated intradermally, the natural route of M.tb infection is through the lung. Excessive lung pathology caused by pulmonary inoculation of BCG has prevented the use of this immunization route. Here, we show that selective chemical treatment of BCG with petroleum ether removes inflammatory lipids from the bacterial surface while keeping BCG viable. Pulmonary vaccination using this modified BCG attenuated inflammatory responses, prevented immunopathology of the lung, and significantly increased protection against M.tb infection in mice. We further directly linked IL-17A as the responsible contributor of improved immunity against M.tb infection. These results provide evidence that selective removal of cytotoxic lipids from the BCG surface attenuates inflammation and offers a safer and superior vaccine against TB causing less damage post-infectious challenge with M.tb.


Assuntos
Vacina BCG/imunologia , Mediadores da Inflamação/imunologia , Lipídeos/imunologia , Pulmão/imunologia , Mycobacterium bovis/fisiologia , Mycobacterium tuberculosis/fisiologia , Tuberculose Pulmonar/imunologia , Alcanos/química , Animais , Vacina BCG/química , Feminino , Mediadores da Inflamação/química , Interleucina-17/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Vacinação
13.
Curr Top Microbiol Immunol ; 420: 283-319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30242513

RESUMO

Lipids perform a wide range of functions inside the cell, ranging from structural building block of membranes and energy storage to cell signaling. The mode of action of many signaling lipids has remained elusive due to their low abundance, high lipophilicity, and inherent instability. Various chemical biology approaches, such as photoaffinity or activity-based protein profiling methods, have been employed to shed light on the biological role of lipids and the lipid-protein interaction profile. In this review, we will summarize the recent developments in the field of chemical probes to study lipid biology, especially in immunology, and indicate potential avenues for future research.


Assuntos
Técnicas Imunológicas/métodos , Metabolismo dos Lipídeos/imunologia , Lipídeos/análise , Lipídeos/imunologia , Lipídeos/química
14.
Xenotransplantation ; 26(2): e12473, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30443967

RESUMO

As outcomes in clinical liver transplantation steadily improve, demand continues to exceed supply, leading to a substantial disparity in organ availability. The translation of porcine liver xenotransplantation (LXT) into a clinical reality aims to address this dilemma. Our laboratory has previously established an applicable model of α-1,3-galactosyltransferase knockout (GalT-KO) pig-to-primate LXT with continuous human coagulation factor infusion and costimulation blockade. This report aims to further investigate the post-LXT lipid and amino acid metabolism profile in our longest surviving recipients (25 and 29 days). Experimental samples and control samples, consisting of pre-transplant porcine and baboon serum and plasma, were analyzed for standard lipid profiles and for amino acid levels. Lipid profiles of LXT recipients remained stable following xenotransplantation compared to donor porcine baseline levels. Amino acid concentrations also remained similar to baseline controls, with the exception of a 3-fold increase in l-ornithine and more than a 10-fold decrease in l-arginine post-transplant when compared to both porcine and baboon baseline levels. The observed changes in l-arginine are consistent with prior studies investigating the effects of graft preservation injury following liver transplantation. These results indicate that the porcine liver can maintain most biochemical profiles stably post-operatively in baboons and suggest that arginine supplementation post-LXT may potentially be useful for further prolongation of xenograft survival.


Assuntos
Aminoácidos/imunologia , Xenoenxertos/imunologia , Lipídeos/imunologia , Transplante de Fígado , Transplante Heterólogo , Animais , Animais Geneticamente Modificados , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos , Fígado/imunologia , Transplante de Fígado/métodos , Papio , Suínos , Transplante Heterólogo/métodos
15.
FASEB J ; 33(3): 3392-3403, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30383446

RESUMO

Allergic conjunctivitis (AC) is one of the most common ocular surface diseases in the world. In AC, T helper type 2 (Th2) immune responses play central roles in orchestrating inflammatory responses. However, the roles of lipid mediators in the onset and progression of AC remain to be fully explored. Although previous reports have shown the beneficial effects of supplementation of ω-3 fatty acids in asthma or atopic dermatitis, the underlying molecular mechanisms are poorly understood. In this study, a diet rich in ω-3 fatty acids alleviated AC symptoms in both early and late phases without affecting Th2 immune responses, but rather by altering the lipid mediator profiles. The ω-3 fatty acids completely suppressed scratching behavior toward the eyes, an allergic reaction provoked by itch. Although total serum IgE levels and the expression levels of Th2 cytokines and chemokines in the conjunctiva were not altered by ω-3 fatty acids, eosinophil infiltration into the conjunctiva was dramatically suppressed. The levels of ω-6-derived proinflammatory lipid mediators, including those with chemoattractant properties for eosinophils, were markedly reduced in the conjunctivae of ω-3 diet-fed mice. Dietary ω-3 fatty acids can alleviate a variety of symptoms of AC by altering the lipid mediator profile.-Hirakata, T., Lee, H.-C., Ohba, M., Saeki, K., Okuno, T., Murakami, A., Matsuda, A., Yokomizo, T. Dietary ω-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses.


Assuntos
Conjuntivite Alérgica/imunologia , Ácidos Graxos Ômega-3/imunologia , Lipídeos/imunologia , Células Th2/imunologia , Animais , Asma/imunologia , Quimiocinas/imunologia , Citocinas/imunologia , Dieta/métodos , Eicosanoides/imunologia , Eosinófilos/imunologia , Feminino , Imunoglobulina E/imunologia , Camundongos , Camundongos Endogâmicos BALB C
16.
Am J Trop Med Hyg ; 100(2): 246-255, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30560773

RESUMO

Current diagnostic tests for visceral leishmaniasis (VL) are either not adapted for use in resource-poor settings or are insufficiently accurate in Eastern Africa. Only the direct agglutination test (DAT), based on whole Leishmania promastigotes, is highly reliable in all endemic regions, but its implementation is hampered by the need for a cold chain, minimal laboratory conditions, and long incubation times. Integrating the DAT antigen(s) in an immunochromatographic rapid diagnostic test (RDT) would overcome these disadvantages. Unfortunately, the identity of the DAT antigen(s) involved in the agglutination reaction is unknown. For this study, we reviewed all publications that might shed some light on this issue. We conclude that the DAT antigen is a mixture of Leishmania-specific epitopes of protein, carbohydrate, and lipid nature. To develop an accurate RDT for VL diagnosis in Eastern Africa, we suggest to complement the classical protein antigen discovery with approaches to identify carbohydrate and lipid epitopes.


Assuntos
Testes de Aglutinação/normas , Antígenos de Protozoários/química , Epitopos/química , Leishmania donovani/química , Leishmania infantum/química , Leishmaniose Visceral/diagnóstico , África Oriental/epidemiologia , Antígenos de Protozoários/imunologia , Carboidratos/química , Carboidratos/imunologia , Epitopos/imunologia , Humanos , Soros Imunes/química , Leishmania donovani/imunologia , Leishmania infantum/imunologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/parasitologia , Lipídeos/química , Lipídeos/imunologia , Proteínas de Protozoários/química , Proteínas de Protozoários/imunologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Biol Trace Elem Res ; 191(1): 199-206, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30515712

RESUMO

A 42-day experiment was conducted to evaluate the influence of dietary copper (Cu) concentrations on growth performance, nutrient digestibility, and serum parameters in broilers aged from 1 to 42 days. Five hundred forty 1-day-old broilers were randomly assigned into 1 of the following 6 dietary treatments: (1) control (basal diet without supplemental Cu), (2) 15 mg/kg supplemental Cu (Cu15), (3) 30 mg/kg supplemental Cu (Cu30), (4) 60 mg/kg supplemental Cu (Cu60), (5) 120 mg/kg supplemental Cu (Cu120), and (6) 240 mg/kg supplemental Cu (Cu240), Cu as copper methionine. A 4-day metabolism trial was conducted during the last week of the experiment feeding. The results showed that dietary Cu supplementation increased the average daily gain and the average daily feed intake (P < 0.01). The feed gain ratio, however, was not affected by dietary Cu (P > 0.10). Additionally, dietary Cu supplementation increased the digestibility of fat and energy (P < 0.05). The concentration of serum cholesterol, triglycerides, and high-density lipoprotein cholesterol decreased with dietary Cu supplementation (P < 0.05). The activities of serum Cu-Zn superoxide dismutase (P < 0.05), glutathione peroxidase (P < 0.05), and ceruloplasmin (P = 0.09), on the contrary, were increased by Cu addition. For immune indexes, dietary Cu supplementation increased serum IgA and IgM (P < 0.05). In addition, the activities of serum ALT increased with increasing dietary Cu supplementation (P < 0.05). In conclusion, our data suggest that Cu supplementation can increase fat digestibility and promote growth. Additionally, dietary Cu supplementation can reduce serum cholesterol and enhance antioxidant capacity in broilers.


Assuntos
Galinhas/crescimento & desenvolvimento , Cobre/farmacologia , Suplementos Nutricionais , Digestão/efeitos dos fármacos , Lipídeos/sangue , Metionina/farmacologia , Ganho de Peso/efeitos dos fármacos , Ração Animal , Animais , Galinhas/imunologia , Digestão/imunologia , Lipídeos/imunologia , Ganho de Peso/imunologia
18.
Int J Mol Sci ; 19(12)2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30558209

RESUMO

Lipids and inflammation regulate each other. Early studies on this topic focused on the systemic effects that the acute inflammatory response-and interleukins-had on lipid metabolism. Today, in the era of the obesity epidemic, whose primary complications are cardio-metabolic diseases, attention has moved to the effects that the nutritional environment and lipid derangements have on peripheral tissues, where lipotoxicity leads to organ damage through an imbalance of chronic inflammatory responses. After an overview of the effects that acute inflammation has on the systemic lipid metabolism, this review will describe the lipid-induced immune responses that take place in peripheral tissues and lead to chronic cardio-metabolic diseases. Moreover, the anti-inflammatory effects of lipid lowering drugs, as well as the possibility of using anti-inflammatory agents against cardio-metabolic diseases, will be discussed.


Assuntos
Inflamação/metabolismo , Interleucinas/metabolismo , Lipídeos/imunologia , Doenças Metabólicas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/metabolismo , Humanos , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Inflamação/tratamento farmacológico , Inflamação/imunologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/imunologia
19.
Int Immunopharmacol ; 65: 580-592, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30447537

RESUMO

Rodent and clinical studies have documented that myeloid cell infiltration of tumors is associated with poor outcomes, neutrophilia and lymphocytopenia. This contrasts with increased lymphocyte infiltration of tumors, which is correlated with improved outcomes. Lifestyle parameters, such as obesity and diets with high levels of saturated fat and/or omega (ω)-6 polyunsaturated fatty acids (PUFAs), can influence these inflammatory parameters, including an increase in extramedullary myelopoiesis (EMM). While tumor secretion of growth factors (GFs) and chemokines regulate tumor-immune-cell crosstalk, lifestyle choices also contribute to inflammation, abnormal pathology and leukocyte infiltration of tumors. A relationship between obesity and high-fat diets (notably saturated fats in Western diets) and inflammation, tumor incidence, metastasis and poor outcomes is generally accepted. However, the mechanisms of dietary promotion of an inflammatory microenvironment and targeted drugs to inhibit the clinical sequelae are poorly understood. Thus, modifications of obesity and dietary fat may provide preventative or therapeutic approaches to control tumor-associated inflammation and disease progression. Currently, the majority of basic and clinical research does not differentiate between obesity and fatty acid consumption as mediators of inflammatory and neoplastic processes. In this review, we discuss the relationships between dietary PUFAs, inflammation and neoplasia and experimental strategies to improve our understanding of these relationships. We conclude that dietary composition, notably the ratio of ω-3 vs ω-6 PUFA regulates tumor growth and the frequency and sites of metastasis that together, impact overall survival (OS) in mice.


Assuntos
Mediadores da Inflamação/imunologia , Lipídeos/imunologia , Células Mieloides/imunologia , Neoplasias/imunologia , Obesidade/imunologia , Animais , Antineoplásicos/uso terapêutico , Dieta Ocidental , Humanos , Imunomodulação , Lipídeos/uso terapêutico , Neoplasias/terapia
20.
Mol Immunol ; 104: 27-36, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30399491

RESUMO

The CD1 family of glycoproteins are MHC class I-like molecules that present a wide array of self and foreign lipid antigens to T-cell receptors (TCRs) on T-cells. Humans express three classes of CD1 molecules, denoted as Group 1 (CD1a, CD1b, and CD1c), Group 2 (CD1d), and Group 3 (CD1e). Of the CD1 family of molecules, CD1b exhibits the largest and most complex antigen binding groove; allowing it the capabilities to present a broad spectrum of lipid antigens. While its role in foreign-lipid presentation in the context of mycobacterial infection are well characterized, understanding the roles of CD1b in autoreactivity are recently being elucidated. While the mechanisms governing proliferation of CD1b-restricted autoreactive T cells, regulation of CD1 gene expression, and the processes controlling CD1+ antigen presenting cell maturation are widely undercharacterized, the exploration of self-lipid antigens in the context of disease have recently come into focus. Furthermore, the recently expanded pool of CD1b crystal structures allow the opportunity to further analyze the molecular mechanisms of T-cell recognition and self-lipid presentation; where the intricacies of the two-compartment system, that accommodate both the presented self-lipid antigen and scaffold lipids, are scrutinized. This review delves into the immunological and molecular mechanisms governing presentation and T-cell recognition of the broad self-lipid repertoire of CD1b; with evidence mounting pointing towards a role in diseases such as microbial infection, autoimmune diseases, and cancer.


Assuntos
Apresentação do Antígeno , Antígenos CD1 , Autoantígenos , Lipídeos , Linfócitos T/imunologia , Animais , Antígenos CD1/química , Antígenos CD1/imunologia , Autoantígenos/química , Autoantígenos/imunologia , Cristalografia por Raios X , Humanos , Lipídeos/química , Lipídeos/imunologia , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA