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BACKGROUND AND AIMS: Zinc (Zn) quantification is of particular interest in many clinical condition (e.g. inflammatory disease, critical care). Currently, Zn status is assessed by measuring plasma/serum concentration. This concentration corresponds to the sum of unbound Zn (Zn-Cu) and Zn highly bound to albumin (Zn-Cb). METHODS: Using a pharmacokinetic approach to the interpretation of total Zn concentration (Zn-Ct), taking into account Zn-Cu and the influence of hypoalbuminemia on Zn-Cb, it is possible to improve the individualization of Zn repletion. RESULTS: Therefore, during pregnancy and in certain inflammatory disease situations, repletion may not be necessary. However, as in critical care, it would be more appropriate to perform Zn-Cu assays to improve Zn repletion. CONCLUSION: Coupled total and unbound Zn should be monitored in order to individualize Zn repletion.
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Cobre , Zinc , Embarazo , Femenino , Humanos , Zinc/metabolismoAsunto(s)
Neovascularización Coroidal/etiología , Conducta Alimentaria , Degeneración Macular/etiología , Estrés Oxidativo/fisiología , Vitaminas/sangre , Anciano , Anciano de 80 o más Años , Antioxidantes/metabolismo , Estudios de Casos y Controles , Neovascularización Coroidal/sangre , Neovascularización Coroidal/epidemiología , Femenino , Francia , Humanos , Estilo de Vida , Degeneración Macular/sangre , Degeneración Macular/epidemiología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Factores de Riesgo , Fumar/epidemiología , Zinc/sangre , beta Caroteno/sangreRESUMEN
BACKGROUND: Fatty acids (FAs) and adipokines such as adiponectin or interleukin-6 (IL-6) are known to modulate inflammation and the development of metabolic syndrome. Whether FA composition assessed in plasma triacylglycerols (TAGs), phospholipids (PLs) and non-esterified fatty acids (NEFAs) and adipose tissue (AT) PLs differed between dysmetabolic and non-dysmetabolic severely obese women remains to be established. Whether the plasma and/or AT arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in the PL sub-fraction may be associated with adipokine AT gene expression needs to be examined. METHODS: FA composition was measured in plasma lipid classes and in the TAG and PL sub-fractions of subcutaneous abdominal and omental ATs of severely obese women paired for age and adiposity but showing a dysmetabolic profile (n = 13) or not (n = 14). FA profile was assessed by gas chromatography. Plasma and AT mRNA concentrations of adiponectin and IL-6 were measured by ELISA and real-time polymerase chain reaction, respectively. RESULTS: Plasma adiponectin and FA concentrations in the NEFA sub-fraction were, respectively, lower and higher in dysmetabolic than in non-dysmetabolic women (p < 0.05). Despite similar FA levels in the PL sub-fraction, the AA/EPA ratio was higher in plasma and ATs (p < 0.005), because of an EPA decrease in plasma and subcutaneous abdominal fat vs. an AA increase in the omental depot. The AA/EPA ratio was negatively associated with adiponectin concentrations in plasma and subcutaneous abdominal AT (0.01 < p < 0.05). CONCLUSIONS: Metabolic dysfunction is associated with a pro-inflammatory phospholipid AA/EPA ratio in plasma and ATs, and an altered adiponectin secretion that could contribute to developing metabolic syndrome.
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Ácidos Araquidónicos/sangre , Ácido Eicosapentaenoico/sangre , Síndrome Metabólico/sangre , Obesidad Mórbida/sangre , Grasa Subcutánea Abdominal/metabolismo , Adulto , Cromatografía de Gases , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-6/sangre , Síndrome Metabólico/etiología , Obesidad Mórbida/complicaciones , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
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Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, ãäT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development (AU)
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Humanos , Linfocitos , Tejido Adiposo Blanco/inmunología , Inmunoterapia/métodos , Inmunidad Innata , Células Presentadoras de Antígenos/inmunología , LeptinaRESUMEN
Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.
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Tejido Adiposo/metabolismo , Linfocitos/metabolismo , Adipoquinas/metabolismo , Animales , Diabetes Mellitus/metabolismo , Humanos , Sistema Inmunológico , Inflamación , Linfocitos/citología , Ratones , Modelos Biológicos , Obesidad/metabolismo , Factores de TiempoRESUMEN
It has been suggested that patients with pulmonary surfactant impairment are more susceptible to Pneumocystis infection than healthy controls. Owing the fact that most patients with pulmonary surfactant impairment also suffer from hypoxia, we explored the effect of intermittent hypobaric hypoxia conditions on the ability of non-immunocompromised rats infected by endotracheal route with P. carinii to clear the infection from their lungs. Control rats, inoculated or not with P. carinii, were maintained in normobaric normoxic conditions, and were submitted or not to dexamethasone administration. It was found that even if hypobaric hypoxia weakened host immune mechanisms and impaired significantly the surfactant composition, mainly of surfactant proteins A and D, these changes were not enough to favour the Pneumocystis growth or to inhibit the clearing of Pneumocystis organisms from the lungs of non-immunocompromised rats. The potential influence of surfactant protein changes on Pneumocystis infection is discussed.
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Hipoxia/metabolismo , Huésped Inmunocomprometido , Neumonía por Pneumocystis/metabolismo , Proteínas Asociadas a Surfactante Pulmonar/metabolismo , Surfactantes Pulmonares/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Pneumocystis carinii/crecimiento & desarrollo , Proteína A Asociada a Surfactante Pulmonar , Proteína D Asociada a Surfactante Pulmonar , Proteínas Asociadas a Surfactante Pulmonar/análisis , Surfactantes Pulmonares/análisis , Ratas , Ratas WistarRESUMEN
Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly altered in obesity. Leptin, production of which is correlated to fat mass, is strongly involved in the relationships between adipose tissues and immune system. We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2) leptin was involved in such relationships. Immunohistological analyses revealed a tight relationship between the T and NK lymphocytes of the stromal vascular fraction and adipocytes. We identified a significant negative and positive correlation between EPI weight and the percentage of NK and total T cells respectively by cytofluorometric analyses. The NK and ancestral gammadelta T cell contents were directly dependent of leptin since they increased significantly in high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to control. By contrast, the alphabeta T cell content seemed independent of leptin because their percentages increased significantly with the EPI weight whatever the type of mice (control, HF, ob/ob). The present study suggests that adipose tissues present, according to their localization, different immunological mechanisms that might be involved in the regulation of adipose cells functions and proliferations.
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Tejido Adiposo/inmunología , Adiposidad/inmunología , Leptina/fisiología , Tejido Adiposo/citología , Animales , Complejo CD3/análisis , Epidídimo/química , Epidídimo/citología , Citometría de Flujo , Inmunohistoquímica , Integrina alfa2/análisis , Células Asesinas Naturales/química , Células Asesinas Naturales/citología , Leptina/genética , Linfocitos/química , Linfocitos/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Leptina , Subgrupos de Linfocitos T/química , Subgrupos de Linfocitos T/citología , Linfocitos T/química , Linfocitos T/citologíaRESUMEN
Close relationships have been demonstrated between adipose tissue and the inflammatory/immune system. Furthermore, obesity is increasingly considered as a state of chronic inflammation. Cytofluorometric analysis reveals the presence of significant levels of lymphocytes in the stroma-vascular fraction of white adipose tissues. In epididymal (EPI) fat, lymphocytes display an "ancestral" immune system phenotype (up to 70% of natural killer (NK), gammadelta+ T and NKT cells among all lymphocytes) whereas the inguinal (ING) immune system presents more adaptive characteristics (high levels of alphabeta+ T and B cells). The percentage of NK cells in EPI fat was decreased in obese mice fed with a high-fat diet, whereas gammadelta positive cells were significantly increased in ING fat. These data support the notion that adipose tissue may elaborate immunological mechanisms to regulate its functions which might be altered in obesity.
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Tejido Adiposo/inmunología , Linfocitos/citología , Obesidad/inmunología , Tejido Adiposo/citología , Animales , Grasas de la Dieta/farmacología , Epidídimo/citología , Masculino , Ratones , Ratones ObesosRESUMEN
The properties of coenzymes Q (CoQ9 and CoQ10) are closely linked to their redox state (CoQox/total CoQ) x 100. In this work, CoQ redox state was biologically validated by high performance liquid chromatography-electrochemical measurement after modulation of mitochondrial electron flow of cultured cells by molecules increasing (rotenone, carbonyl cyanide chlorophenylhydrazone) or decreasing (antimycin) CoQ oxidation. The tissue specificity of CoQ redox state and content were investigated in control and hypoxic rats. In control rats, there was a strong negative linear regression between tissular CoQ redox state and CoQ content. Hypoxia increased CoQ9 redox state and decreased CoQ9 content in a negative linear relationship in the different tissues, except the heart and lung. This result demonstrates that, under conditions of mitochondrial impairment, CoQ redox control is tissue-specific.
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Mitocondrias/metabolismo , Ubiquinona/metabolismo , Células 3T3 , Animales , Cromatografía Líquida de Alta Presión , Transporte de Electrón/fisiología , Hipoxia/metabolismo , Masculino , Ratones , Oxidación-Reducción , Estrés Oxidativo , Ratas , Ratas Wistar , Análisis de Regresión , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución Tisular , Ubiquinona/químicaAsunto(s)
Cromatografía Líquida de Alta Presión/métodos , Leucina/sangre , Enfermedad de la Orina de Jarabe de Arce/sangre , Enfermedad de la Orina de Jarabe de Arce/diagnóstico , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión/economía , Cromatografía Líquida de Alta Presión/normas , Progresión de la Enfermedad , Nutrición Enteral , Hemodiafiltración , Humanos , Lactante , Recién Nacido , Enfermedad de la Orina de Jarabe de Arce/clasificación , Enfermedad de la Orina de Jarabe de Arce/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
TNF-alpha is a pleiotropic cytokine activating several signaling pathways initiated at distinct intracellular domains of the TNF receptors. Although the C-terminal region is believed to be responsible for apoptosis induction, the functions of more membrane-proximal domains, including the domain that couples to neutral sphingomyelinase activation, are not yet fully elucidated. The roles of this region and of the associated adapter protein FAN (factor associated with neutral SMase activation) in the cytotoxic response to TNF have been investigated. We have now shown that stable expression in human fibroblasts of a dominant negative form of FAN abrogates TNF-induced ceramide generation from sphingomyelin hydrolysis and reduces caspase processing, thus markedly inhibiting TNF-triggered apoptosis. However, the cytotoxic responses to daunorubicin and exogenous ceramide remain unaltered, as do the TNF-induced p42/p44 MAPK activation and CD54 expression. Fibroblasts from FAN-knockout mice also proved to be resistant to TNF toxicity. These findings highlight the previously unrecognized role of the adapter protein FAN in signaling cell death induction by TNF.
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Apoptosis/fisiología , Proteínas/fisiología , Factor de Necrosis Tumoral alfa/fisiología , Clorometilcetonas de Aminoácidos/farmacología , Animales , Antígenos CD/efectos de los fármacos , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Línea Celular Transformada , Células Cultivadas/efectos de los fármacos , Ceramidas/biosíntesis , Ceramidas/farmacología , Inhibidores de Cisteína Proteinasa/farmacología , Daunorrubicina/farmacología , Activación Enzimática/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Genes Dominantes , Humanos , Hidrólisis , Molécula 1 de Adhesión Intercelular/biosíntesis , Molécula 1 de Adhesión Intercelular/genética , Péptidos y Proteínas de Señalización Intracelular , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Ratones Noqueados , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Estructura Terciaria de Proteína , Proteínas/genética , Receptores del Factor de Necrosis Tumoral/efectos de los fármacos , Receptores Tipo I de Factores de Necrosis Tumoral , Proteínas Recombinantes de Fusión/fisiología , Sistemas de Mensajero Secundario , Esfingomielina Fosfodiesterasa/metabolismo , Esfingomielinas/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Factor de Necrosis Tumoral alfa/toxicidad , Células U937RESUMEN
Recently, it was demonstrated that CD8(+) T cells are important for the response against Chlamydia pneumoniae. By use of the human monocytic cell line U937 and human monocytes taken from peripheral blood, we investigated the effect of infection on various molecules critical for CD8(+) T cell function. A strong secretion of interleukin (IL)-10 by infected cells was observed, together with an inhibited expression of major histocompatibility complex (MHC) class I antigens, but without significant alteration of tumor growth factor-beta secretion or MHC class II expression. Recombinant IL-10 added to uninfected U937 cells decreased the expression of MHC class I, whereas blocking antibodies to IL-10 and its receptor abolished the C. pneumoniae-induced inhibition of MHC class I expression. Analysis of our data provides evidence that IL-10 secretion induced by C. pneumoniae infection of monocytic cells down-regulates the expression of MHC class I molecules and thereby might reduce the presentation of bacterial epitopes by MHC. This would decrease the ability of CD8(+) T cells to eliminate infected cells.
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Chlamydophila pneumoniae/fisiología , Antígenos de Histocompatibilidad Clase I/biosíntesis , Interleucina-10/biosíntesis , Antígenos CD18/biosíntesis , Regulación hacia Abajo , Humanos , Molécula 1 de Adhesión Intercelular/biosíntesis , Monocitos/metabolismo , Monocitos/microbiología , Factor de Crecimiento Transformador beta/biosíntesis , Células U937Asunto(s)
División Celular/fisiología , Regulación de la Expresión Génica , Linfocitos/citología , Músculo Liso Vascular/citología , Músculo Liso Vascular/fisiología , Animales , Bovinos , Células Cultivadas , Medios de Cultivo Condicionados , Citocinas/análisis , Citocinas/biosíntesis , Prueba de Histocompatibilidad , Humanos , Prueba de Cultivo Mixto de Linfocitos , Linfocitos/inmunología , Trasplante HomólogoRESUMEN
Oxidized low density lipoproteins (oxLDLs) and activated T lymphocytes are present in early atherosclerotic plaques. It has been shown that oxLDLs are cytotoxic to cultured vascular cells but their possible toxic action on T lymphocytes has not been described. Peripheral blood lymphocytes from healthy individuals were stimulated in vitro with the polyclonal activator phytohemagglutinin and treated with various doses of native and mildly oxidized LDLs. Low doses of oxLDLs inhibited cell growth and DNA synthesis after 48 h culture and at 200 microg apoB/ml we observed a loss of cell viability. Dead cells did not exhibit significant increase of alteration of membrane integrity (i.e., necrosis) but showed chromatin fragmentation evaluated by DNA staining with 4', 6-diamidino-2-phenylindole and propidium iodide. This fragmentation increased with TBARS and hydroperoxide levels. The expression of early apoptosis marker Apo2.7 rose among the CD3(+) T-cell population. In addition, morphological analysis showed apoptotic features (cell shrinking, nucleus condensation, and fragmentation). Study of phosphatidylserine expression using Annexin V confirmed that oxLDLs induced apoptosis in activated lymphocytes. In the Jurkat T-cell line cultured with oxLDLs, apoptotic morphological changes (condensation and nucleus fragmentation) were observed and they were accompanied by DNA fragmentation visualized by propidium iodide staining and electrophoresis showing apoptotic ladder. These results demonstrate that mildly oxidized LDLs induce apoptosis in a part of activated and proliferating T cells. T-lymphocyte apoptosis induction in atherosclerotic lesions might contribute to the development of an inappropriate local T cell response.
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Apoptosis , Lipoproteínas LDL/fisiología , Fitohemaglutininas/farmacología , Linfocitos T/fisiología , División Celular , Supervivencia Celular , Humanos , Células Jurkat , Microscopía Fluorescente , Oxidación-Reducción , Linfocitos T/efectos de los fármacosRESUMEN
Activated T-lymphocytes are found early in atherosclerosis lesions, but little is known about their role. Oxidized low-density lipoproteins (oxLDLs) are considered to be involved in the pathogenesis of the lesions, and we have previously demonstrated that oxLDLs inhibit not only interleukin (IL)-2-receptor expression on the surface of in vitro-activated T-lymphocytes but also their proliferation. We have now investigated the effect of oxLDLs on blast differentiation, on IL-2 synthesis and on the activation of the nuclear factor kappaB (NF-kappaB) system in activated lymphocytes. Mildly oxLDLs (50 and 100 microgram/ml) decreased the number of lymphoblasts and the level of IL-2 concentration in the culture supernatants after activation of lymphocytes by phytohaemagglutinin and PMA+ionomycin. The inhibition of IL-2 production was observed in the CD3(+) T-lymphocyte cytoplasm as early as 4 h after activation by PMA+ionomycin. The study of NF-kappaB showed that oxLDLs led to a decrease of activation-induced p65/p50 NF-kappaB heterodimer binding to DNA, whereas the presence of the constitutive nuclear form of p50 dimer was unchanged. This was correlated with an unchanged level of the active form of the cytosolic inhibitor protein IkappaB-alpha. Taken together, these observations suggest that the immunosuppressive effect of oxLDLs might operate via a dysregulation of the T-lymphocyte activation mechanisms.
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Interleucina-2/metabolismo , Lipoproteínas LDL/farmacología , Activación de Linfocitos , FN-kappa B/metabolismo , Linfocitos T/metabolismo , Arteriosclerosis/etiología , Diferenciación Celular , Células Cultivadas , ADN/metabolismo , Citometría de Flujo , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Humanos , Técnicas para Inmunoenzimas , Oxidación-Reducción , Unión Proteica , Linfocitos T/citologíaRESUMEN
Oxidized low density lipoproteins (oxLDL) are thought to play a central role in the development of atherosclerosis. Toxic concentrations of mildly oxidized LDL elicit massive apoptosis of endothelial cells (Escargueil-Blanc, I., Meilhac, O., Pieraggi, M. T. , Arnal J. F., Salvayre, R., Nègre-Salvayre, A. (1997) Arterioscler. Thromb. Vasc. Biol. 17, 331-339). Since the lipid mediator ceramide emerged as a potent inducer of apoptosis, we aimed at investigating the occurrence of ceramide formation and its potential role in oxLDL-induced apoptosis. In ECV-304 endothelial cells, toxic concentrations of oxLDL triggered an early activation of the sphingomyelin-ceramide pathway, as shown by both sphingomyelin hydrolysis and ceramide formation. N-Tosyl-L-phenylalanyl chloromethyl ketone (TPCK) and dichloroisocoumarin (DCIC), two serine-protease inhibitors (serpins), blocked the oxLDL-induced ceramide generation but, unexpectedly, did not inhibit the oxLDL-induced apoptosis. Conversely, treatment of endothelial cells by bacterial sphingomyelinase, under conditions effectively generating ceramide, did not induce apoptosis. In contrast, short-chain permeant C2- and C6-ceramides elicited apoptosis of ECV-304. However, the mechanisms of apoptosis triggered by C2-ceramide and by oxLDL were (at least in part) different, because C2-ceramide-induced apoptosis was calcium-independent, whereas oxLDL-induced apoptosis was calcium-dependent. In conclusion, it is suggested that oxLDL-induced apoptosis is calcium-dependent but independent of the activation of the sphingomyelin-ceramide pathway and that the toxic effect of short chain permeant ceramides is calcium-independent and does not mimic the effect of natural ceramides induced by oxLDL.
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Apoptosis , Ceramidas/metabolismo , Endotelio Vascular/efectos de los fármacos , Lipoproteínas LDL/toxicidad , Esfingomielinas/metabolismo , Arteriosclerosis/etiología , Calcio/metabolismo , División Celular , Línea Celular , Ceramidas/toxicidad , Humanos , Hidrólisis , Inhibidores de Serina Proteinasa/farmacología , Transducción de Señal , Esfingomielina Fosfodiesterasa/farmacología , Esfingosina/análogos & derivados , Esfingosina/toxicidad , Venas Umbilicales/citologíaRESUMEN
Activated T-lymphocytes are present in early atherosclerotic lesions where they may interact with oxidized low-density lipoproteins (oxLDLs). In this study the non-specific effect of oxLDLs on the activation of T-cells in vitro was investigated. LDLs were oxidized by UV irradiation and characterized by a low level of lipid peroxidation and only slight apolipoprotein B modification. Peripheral blood lymphocytes from normal individuals were stimulated in vitro with the polyclonal activator phytohaemagglutinin in the presence of various doses of LDLs and oxLDLs. LDLs enhanced the proliferation of peripheral blood lymphocytes at doses up to 100 microg/ml but were inhibitory at 200 microg/ml, whereas low doses of oxLDLs (over 10 microg/ml) inhibited the proliferation. OxLDLs also inhibited the proliferative responses of an alloreactive CD4+ T-cell line immortalized by Herpes virus saimiri and an influenza haemagglutinin-specific CD4+ T-cell clone. Viability tests using Trypan Blue exclusion or expression of Apo2.7, an apoptosis marker, did not indicate any significant cell death at doses up to 100 microg/ml oxLDL. At this concentration, cell-cycle analysis showed an accumulation of cells at the G1/S interface in the CD4+ cell clone, without significant DNA fragmentation. The expression of the activation antigen CD25 on T-lymphocytes (on phytohaemagglutinin-activated T-cells and on CD4+ T-cell clone), requisite to the commitment of activated T-cells from G1 phase to S phase, was also inhibited by oxLDLs whereas expression of other activation antigens such as CD69 and HLA-DR was unchanged. In conclusion, these data show that mildly oxidized LDLs inhibit the proliferation and CD25 expression of activated T-lymphocytes and suggest that oxLDLs may slow down the T-cell response in atherosclerotic lesions.
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Linfocitos T CD4-Positivos/citología , Lipoproteínas LDL/metabolismo , Receptores de Interleucina-2/metabolismo , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , División Celular , Células Cultivadas , Humanos , Activación de Linfocitos/efectos de los fármacos , Oxidación-Reducción , Fitohemaglutininas/farmacología , Timidina/metabolismoRESUMEN
Human lymphocytes derived from the peripheral blood of a healthy woman were transfected with a plasmid carrying the simian virus 40 (SV40) large T antigen. The successfully transformed cells contained SV40 large T DNA and were negative for Epstein-Barr virus (EBV) and human T-cell leukaemia virus (HTLV)-1 genomes. The immortalized cell line was assigned to the T-lymphocyte lineage on the basis of morphological, immunological and cytochemical criteria. While the cells expressed CD1a and CD4 at the cell surface, the CD3 complex was solely intracytoplasmic. Immunoprecipitation studies indicated that these cells lacked T-cell receptor (TCR) alpha-chains but not beta-chains. They were negative for activation markers such as CD25, CD69 and major histocompatibility (MHC) class II molecules. In addition, the transformed cells exhibited a complete growth independency towards interleukin-2 (IL-2). However, after phorbol ester stimulation, CD25 and CD69 markers were expressed and IL-2 was secreted. This new human immortalized T-lymphocytic cell line, which is cell-surface TCR/CD3-negative, may be useful as an in vitro model for studying TCR/CD3 assembly, expression and signal transduction.