RESUMEN
Neutrophils are widely known as proinflammatory cells associated with tissue damage and for their early arrival at sites of infection, where they exert their phagocytic activity, release their granule contents, and subsequently die. However, this view has been challenged by emerging evidence that neutrophils have other activities and are not so short-lived. Following activation, neutrophil effector functions include production and release of granule contents, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). Neutrophils have also been shown to produce a wide range of cytokines that have pro- or anti-inflammatory activity, adding a modulatory role for this cell, previously known as a suicide effector. The presence of cytokines almost always implies intercellular modulation, potentially unmasking interactions of neutrophils with other immune cells. In fact, neutrophils have been found to help B cells and to modulate dendritic cell (DC), macrophage, and T-cell activities. In this review, we describe some ways in which neutrophils influence the inflammatory environment in infection, cancer, and autoimmunity, regulating both innate and adaptive immune responses. These cells can switch phenotypes and exert functions beyond cytotoxicity against invading pathogens, extending the view of neutrophils beyond suicide effectors to include functions as regulatory and suppressor cells.
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Humanos , Inmunidad Adaptativa/inmunología , Plasticidad de la Célula/inmunología , Inmunomodulación/inmunología , Activación Neutrófila/inmunología , Neutrófilos/fisiología , Enfermedades del Sistema Inmune/inmunología , Inflamación/inmunología , Neoplasias/inmunología , Neutrófilos/inmunologíaRESUMEN
Neutrophils are widely known as proinflammatory cells associated with tissue damage and for their early arrival at sites of infection, where they exert their phagocytic activity, release their granule contents, and subsequently die. However, this view has been challenged by emerging evidence that neutrophils have other activities and are not so short-lived. Following activation, neutrophil effector functions include production and release of granule contents, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). Neutrophils have also been shown to produce a wide range of cytokines that have pro- or anti-inflammatory activity, adding a modulatory role for this cell, previously known as a suicide effector. The presence of cytokines almost always implies intercellular modulation, potentially unmasking interactions of neutrophils with other immune cells. In fact, neutrophils have been found to help B cells and to modulate dendritic cell (DC), macrophage, and T-cell activities. In this review, we describe some ways in which neutrophils influence the inflammatory environment in infection, cancer, and autoimmunity, regulating both innate and adaptive immune responses. These cells can switch phenotypes and exert functions beyond cytotoxicity against invading pathogens, extending the view of neutrophils beyond suicide effectors to include functions as regulatory and suppressor cells.
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Inmunidad Adaptativa/inmunología , Plasticidad de la Célula/inmunología , Inmunomodulación/inmunología , Activación Neutrófila/inmunología , Neutrófilos/fisiología , Humanos , Enfermedades del Sistema Inmune/inmunología , Inflamación/inmunología , Neoplasias/inmunología , Neutrófilos/inmunologíaRESUMEN
OBJECTIVE: Circulating monocytes adhere to the endothelium and migrate into the intima contributing to atherosclerotic plaque growth. Cigarette smoke is a risk factor for atherosclerosis, but it is not completely known how it affects monocyte behavior in atherogenesis. METHODS: We studied the effects of cigarette smoke condensate (CSC) on human monocytes (HM) chemotaxis and transmigration through an endothelial cell (EC) monolayer. RESULTS: Pre-treatment with CSC caused a decrease in HM chemotaxis and transmigration (-55% and -18% vs control, p < 0.05, respectively), paralleled by a reduced expression of Rac 1 GTPase. On the contrary, direct exposure of both HM and EC to CSC increased (+23% vs control, p < 0.05) HM transmigration, paralleled by a strong stimulation of VCAM1 and ICAM1 expression by ECs, and by a slight increase in monocyte integrin expression. An enhancement of monocyte transmigration was obtained after the exposure of both HM and EC to medium conditioned by HM previously incubated with CSC (+265% vs control, p < 0.001). CSC showed a stimulatory effect on the expression by HM of TLR4, MCP1, IL8, IL1beta, and TNFalfa, which was ablated by pre treatment with PDTC. Incubation with neutralizing antibodies against both MCP1 or IL8 completely abolished the CSC-conditioned medium induced HM transmigration. CONCLUSIONS: CSC induces HM to release chemotactic factor(s), which amplify the recruitment and transmigration of inflammatory cells through EC, but CSC may also reduce HM migratory capacity. Therefore, exposure to CSC affects monocyte behavior and interaction with the endothelium, thus potentially facilitating and/or further aggravating the atherogenic process.
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Quimiotaxis de Leucocito/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Monocitos/efectos de los fármacos , Humo/efectos adversos , Fumar/efectos adversos , Migración Transendotelial y Transepitelial/efectos de los fármacos , Línea Celular , Quimiocina CCL2/metabolismo , Técnicas de Cocultivo , Medios de Cultivo Condicionados/metabolismo , Relación Dosis-Respuesta a Droga , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Monocitos/inmunología , Monocitos/metabolismo , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Proteína de Unión al GTP rac1/metabolismoRESUMEN
The participation of regulatory T (Treg) cells in B cell-induced T cell tolerance has been claimed in different models. In skin grafts, naive B cells were shown to induce graft tolerance. However, neither the contribution of Treg cells to B cell-induced skin tolerance nor their contribution to the histopathological diagnosis of graft acceptance has been addressed. Here, using male C57BL/6 naive B cells to tolerize female animals, we show that skin graft tolerance is dependent on CD25+ Treg cell activity and independent of B cell-derived IL-10. In fact, B cells from IL-10-deficient mice were able to induce skin graft tolerance while Treg depletion of the host inhibited 100% graft survival. We questioned how Treg cell-mediated tolerance would impact on histopathology. B cell-tolerized skin grafts showed pathological scores as high as a rejected skin from naive, non-tolerized mice due to loss of skin appendages, reduced keratinization and mononuclear cell infiltrate. However, in tolerized mice, 40% of graft infiltrating CD4+ cells were FoxP3+ Treg cells with a high Treg:Teff (effector T cell) ratio (6:1) as compared to non-tolerized mice where Tregs comprise less than 8% of total infiltrating CD4 cells with a Treg:Teff ratio below 1:1. These results render Treg cells an obligatory target for histopathological studies on tissue rejection that may help to diagnose and predict the outcome of a transplanted organ.
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Linfocitos B/inmunología , Supervivencia de Injerto/inmunología , Trasplante de Piel , Linfocitos T Reguladores/inmunología , Tolerancia al Trasplante/inmunología , Animales , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Factores de TiempoRESUMEN
Of the over 400 known exoplanets, there are about 70 planets that transit their central star, a situation that permits the derivation of their basic parameters and facilitates investigations of their atmospheres. Some short-period planets, including the first terrestrial exoplanet (CoRoT-7b), have been discovered using a space mission designed to find smaller and more distant planets than can be seen from the ground. Here we report transit observations of CoRoT-9b, which orbits with a period of 95.274 days on a low eccentricity of 0.11 +/- 0.04 around a solar-like star. Its periastron distance of 0.36 astronomical units is by far the largest of all transiting planets, yielding a 'temperate' photospheric temperature estimated to be between 250 and 430 K. Unlike previously known transiting planets, the present size of CoRoT-9b should not have been affected by tidal heat dissipation processes. Indeed, the planet is found to be well described by standard evolution models with an inferred interior composition consistent with that of Jupiter and Saturn.
RESUMEN
A number of in vitro and in vivo studies using selective agonists have indicated a neuroprotective role for group-II metabotropic glutamate (mGlu2/3) receptors in various models of neuronal injury. Although an interplay among neurotrophic factors and mGlu2/3 receptors signalling system has been suggested as possible mechanism involved on neuroprotection, at present poor information are available concerning the in vivo regulation by mGlu2/3 receptors activation of specific neurotrophic factors. By using in situ hybridization and western blotting methods the aim of present study was to analyse the potential regulatory role of selective mGluR2/3 agonist LY379268 treatment on brain derived neurotrophic factor (BDNF) expression in the mouse brain. The treatment with LY379268 evidenced a significant upregulation of BDNF mRNA levels in the cerebral cortex and in the hippocampal formation with a peak at 3 h from treatment and its disappearance already at 6 h from treatment. An analysis of dose-effect curve revealed that LY379268 may significantly enhance BDNF mRNA expression already at dose of 0.250 mg/kg b.w. The upregulation of BDNF mRNA expression was followed by a significant increase of BDNF protein levels at 24 h from LY379268 treatment. These effects of LY379268 treatment on BDNF expression were restricted to neuronal cells and were blocked by the new selective mGlu2/3 receptor antagonist LY341495, suggesting a receptor specificity. Taken together these findings suggest that several previous observed neuroprotective and trophic actions of mGluR2/3 agonists treatment may be mediated, at least in the cerebral cortex and hippocampal formation, by upregulation of BDNF expression.
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Aminoácidos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Agonistas de Aminoácidos Excitadores/farmacología , Receptores de Glutamato Metabotrópico/agonistas , Aminoácidos/administración & dosificación , Animales , Encéfalo/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Relación Dosis-Respuesta a Droga , Agonistas de Aminoácidos Excitadores/administración & dosificación , Antagonistas de Aminoácidos Excitadores/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/metabolismo , ARN Mensajero/metabolismo , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Receptores de Glutamato Metabotrópico/metabolismo , Factores de Tiempo , Regulación hacia Arriba/efectos de los fármacos , Xantenos/farmacologíaRESUMEN
Neurogenesis occurs in two regions of the adult brain, namely, the subventricular zone (SVZ) throughout the wall of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG) in hippocampal formation. Adult neurogenesis requires several neurotrophic factors to sustain and regulate the proliferation and differentiation of the adult stem cell population. In the present review, we examine the cellular and functional aspects of a trophic system mediated by fibroblast growth factor-2 (FGF-2) and its receptors (FGFRs) related to neurogenesis in the SVZ and SGZ of the adult rat brain. In the SVZ, FGF-2 is expressed in GFAP-positive cells of SVZ but is not present in proliferating precursor cells, which instead express FGFR-1 and FGFR-2, but not FGFR-3 mRNA, although expressed in the SVZ, and FGFR-4. Therefore, it seems that in the SVZ FGF-2 may be released by GFAP-positive cells, different from the precursor cell lineage, and via volume transmission it reaches the proliferating precursor cells. FGFR-1 mRNA is also expressed in the SGZ and is localized in BrdU-labeled precursor cells, whereas FGFR-2 and FGFR-3 mRNA, although expressed in the SGZ, are not located within proliferating precursor cells. An aged-related decline of proliferating precursor cells in the SVZ and DG of old rats has been well documented, and there is the suggestion that in part it could be the consequence of alterations in growth factor expression levels. Thus, the old precursors may respond to growth factors, suggesting that during aging the basic components for neuronal precursor cell proliferation are retained and the capacity to increase neurogenesis after appropriate stimulation is still preserved. In conclusion, the trophic system mediated by FGF-2 and its receptors contributes to create an important micro-environmental niche that promotes neurogenesis in the adult and aged brain.
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Encéfalo/fisiología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Neurogénesis/fisiología , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Envejecimiento , Animales , Ventrículos Cerebrales/fisiología , Humanos , Transducción de SeñalRESUMEN
INTRODUCTION: Polymorphonuclear neutrophil (PMN) dysfunctions have been associated with severe forms of periodontitis. This study evaluated the correlation between PMN phagocytosis and oxidative burst with the subgingival microbiota of patients with generalized aggressive periodontitis (GAgP). METHODS: Heparinized peripheral blood samples were obtained from 18 GAgP patients and 11 periodontally healthy (PH) subjects, and PMNs were isolated on a Ficoll-Hypaque gradient. For phagocytosis analysis, PMNs were incubated with fluorescein-labeled Staphylococcus aureus. The oxidative burst was evaluated by incubation of PMNs with dihydroethidium and activation by S. aureus. The assays were examined using flow cytometry. Subgingival biofilm samples were obtained from periodontal sites with and without periodontitis and 24 species were detected by checkerboard. RESULTS: A significantly lower phagocytosis rate was observed for patients with GAgP compared with PH subjects over time (P < 0.05). No differences between groups were found for superoxide production. GAgP patients presented significantly higher prevalence and levels of Porphyromonas gingivalis, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans serotype b than controls (P < 0.05). Significant negative correlations between T. forsythia and P. gingivalis and PMN functions were observed. CONCLUSIONS: GAgP subjects presented diminished phagocytic activity of peripheral PMNs and high prevalence and levels of classical periodontal pathogens.
Asunto(s)
Periodontitis Agresiva/inmunología , Periodontitis Agresiva/microbiología , Neutrófilos/inmunología , Bolsa Periodontal/microbiología , Adulto , Aggregatibacter actinomycetemcomitans/inmunología , Aggregatibacter actinomycetemcomitans/aislamiento & purificación , Bacteroides/inmunología , Bacteroides/aislamiento & purificación , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Humanos , Masculino , Fagocitosis , Porphyromonas gingivalis/inmunología , Porphyromonas gingivalis/aislamiento & purificación , Estallido Respiratorio , Streptococcus/inmunología , Streptococcus/aislamiento & purificaciónRESUMEN
Polymorphisms in genes encoding folate metabolizing enzymes have been linked to an increased risk of maternal chromosomal nondisjunction in several populations. With the purpose of evaluating this relationship, we compared the frequencies of 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and 66A>G in the methionine synthase reductase gene (MTRR) between 103 young mothers of Down syndrome (DS) individuals and 108 control mothers, whose offspring was karyotypically normal, correlating it with an estimative of folate and - related micronutrients levels intake. Maternal and paternal transmission frequencies of MTHFR 677T allele were also examined to access potential parent-of-origin effects. PCR-RFLP for genomic DNA was accomplished and allele/genotype frequencies differences were determined using the x(2) test, whereas pattern of transmission of the MTHFR 677 allele was analyzed by transmission disequilibrium test. None of the polymorphisms seemed to be more frequent in case mothers than in controls, either individually or combined. The estimative of nutritional intake revealed that folate consumption median was inadequate in both groups, whereas methionine and zinc consumption medians were significantly greater in control mothers. It suggests that such interaction between genetic profile and environment could predispose this sub group of women to have a DS child. Additional studies focusing the interaction between nutritional intakes, biochemical data and folate pathway polymorphisms are needed to confirm the present results. The possibility of neutralize the biochemical negative effects of folate-related polymorphisms through oral supplementation could provide new targets for DS prevention.
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Síndrome de Down/etiología , Síndrome de Down/genética , Ácido Fólico/metabolismo , Desnutrición/complicaciones , Desnutrición/metabolismo , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Síndrome de Down/metabolismo , Femenino , Ferredoxina-NADP Reductasa/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Recién Nacido , Masculino , Desnutrición/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Madres , Polimorfismo de Nucleótido Simple , Embarazo , Factores de Riesgo , Adulto JovenRESUMEN
Two different levels of control for bone marrow hematopoiesis are believed to exist. On the one hand, normal blood cell distribution is believed to be maintained in healthy subjects by an "innate" hematopoietic activity, i.e., a basal intrinsic bone marrow activity. On the other hand, an "adaptive" hematopoietic state develops in response to stress-induced stimulation. This adaptive hematopoiesis targets specific lineage amplification depending on the nature of the stimuli. Unexpectedly, recent data have shown that what we call "normal hematopoiesis" is a stress-induced state maintained by activated bone marrow CD4+ T cells. This T cell population includes a large number of recently stimulated cells in normal mice whose priming requires the presence of the cognate antigens. In the absence of CD4+ T cells or their cognate antigens, hematopoiesis is maintained at low levels. In this review, we summarize current knowledge on T cell biology, which could explain how CD4+ T cells can help hematopoiesis, how they are primed in mice that were not intentionally immunized, and what maintains them activated in the bone marrow.
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Animales , Humanos , Células de la Médula Ósea/citología , /inmunología , Hematopoyesis/inmunología , Memoria Inmunológica/inmunología , Células de la Médula Ósea/inmunología , /fisiología , Inmunidad Celular/fisiología , Inmunidad Innata/fisiología , Memoria Inmunológica/fisiologíaRESUMEN
Two different levels of control for bone marrow hematopoiesis are believed to exist. On the one hand, normal blood cell distribution is believed to be maintained in healthy subjects by an "innate" hematopoietic activity, i.e., a basal intrinsic bone marrow activity. On the other hand, an "adaptive" hematopoietic state develops in response to stress-induced stimulation. This adaptive hematopoiesis targets specific lineage amplification depending on the nature of the stimuli. Unexpectedly, recent data have shown that what we call "normal hematopoiesis" is a stress-induced state maintained by activated bone marrow CD4+ T cells. This T cell population includes a large number of recently stimulated cells in normal mice whose priming requires the presence of the cognate antigens. In the absence of CD4+ T cells or their cognate antigens, hematopoiesis is maintained at low levels. In this review, we summarize current knowledge on T cell biology, which could explain how CD4+ T cells can help hematopoiesis, how they are primed in mice that were not intentionally immunized, and what maintains them activated in the bone marrow.
Asunto(s)
Células de la Médula Ósea/citología , Linfocitos T CD4-Positivos/inmunología , Hematopoyesis/inmunología , Memoria Inmunológica/inmunología , Animales , Células de la Médula Ósea/inmunología , Linfocitos T CD4-Positivos/fisiología , Humanos , Inmunidad Celular/fisiología , Inmunidad Innata/fisiología , Memoria Inmunológica/fisiologíaRESUMEN
AIM: Axillary dissection may be avoided in patients with breast cancer and negative sentinel lymph node (SL); not all metastatic SL patients show metastasis on the remaining axillary lymph nodes. The purpose of this study was to evaluate the possible presence of metastases in the remaining axillary lymphatic glands, the so called not-SL, in patients with SL either macro- or micrometastatic, and to try to locate a subgroup of patients in which metastases are present only in SL. METHODS: A retrospective study was conducted in 91 patients who from March 2000 to June 2003 underwent a biopsy of SL and dissection of the axillary cavity (23 patients with micrometastatic SL and 68 with macrometastatic SL). A multivariate analysis evaluated the statistic association with not-SL metastases of almost 22 prognostic factors. RESULTS: Of the 68 patients affected by macrometastatic SL, 32 (47%) showed metastases of the not-SL; of the 23 patients with micrometastatic SL, 7 (30%) showed metastases of the not-SL. In the last 2 years, among all those patients with micrometastatic SL, the probability of disease at the not-SL reached the null percentage. During year 2000, 3 (50%) patients out of 6 with micrometastatic SL showed metastases at the not-SL; during years 2002/2003 no patients out of 8 with micrometastatic SL showed metastases at the not-SL. A multivariate analysis showed only 2 factors significantly associated to the metastatic not-SL: age (cut off 60 years) OR 4.6, P 0.003 and histological examination of the SL OR 2.8, P 0.003. CONCLUSIONS: The average frequency of disease of not-SL in patients with either micro- or macrometastatic SL is not so different than values observed in literature. The predictive disease value of the remaining axillary lymphatic glands of the micrometastatic SL reached the null percentage in the last 2 years, therefore at seems to depend on the operators experience in SL biopsy technique. Among patients with metastatic SL (micro and macro), it was not possible to detect a subgroup in which not-SL are not metastatic with reasonable certainty. Nevertheless, a multivariate analysis showed the histological factor of the SL, to be significantly associated to not-SL metastases, as well as to the age-factor.
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Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane--an early hallmark of apoptosis--and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.
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Apoptosis/fisiología , Leishmania/fisiología , Fosfatidilserinas/fisiología , Animales , Apoptosis/inmunología , Arginasa/metabolismo , Interacciones Huésped-Parásitos/inmunología , Interacciones Huésped-Parásitos/fisiología , Sistema Inmunológico/fisiología , Leishmania/inmunología , Macrófagos/fisiología , Fosfatidilserinas/inmunologíaRESUMEN
Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane - an early hallmark of apoptosis - and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.
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Animales , Apoptosis/fisiología , Leishmania/fisiología , Fosfatidilserinas/fisiología , Apoptosis/inmunología , Arginasa/metabolismo , Interacciones Huésped-Parásitos/inmunología , Interacciones Huésped-Parásitos/fisiología , Sistema Inmunológico/fisiología , Leishmania/inmunología , Macrófagos/fisiología , Fosfatidilserinas/inmunologíaRESUMEN
Normal and leukemic blood cell progenitors depend upon the bone marrow (BM) stroma with which they communicate through soluble and membrane-anchored mediators, adhesive interactions and gap junctions (GJ). Regarding hematopoiesis, it is believed that it can be influenced by connexin expression, but the exact role of GJ in cell death and proliferation is not clear. Using flow cytometry, we monitored the division rate of leukemic cell lines, communicating and not communicating with stromal cell line through GJ. We found that GJ-coupled cells (i) did not proliferate; (ii) were kept in G0; and (iii) were protected from drug-induced apoptosis when compared to either total or uncoupled cell population. We conclude that GJ coupling between stroma and leukemic lymphoblasts prevents proliferation, keeping cells in a quiescent state, thus increasing their resistance to antimitotic drugs. Since GJ are particularly abundant in the sub-endosteal environment, which harbors blood stem cells, we also asked which cells within the normal human BM communicate with the stroma. Using a primary BM stroma cell culture, our results show that 80% of CD34+ progenitors communicate through GJ. We propose that blood cell progenitors might be retained in the low-cycling state by GJ-mediated communication with the hematopoietic stroma.
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Apoptosis , Células de la Médula Ósea/citología , Comunicación Celular , Uniones Comunicantes/fisiología , Leucemia/patología , Células del Estroma/fisiología , Antígenos CD34/análisis , División Celular , Línea Celular Tumoral , Técnicas de Cocultivo , Células Madre Hematopoyéticas/química , Células Madre Hematopoyéticas/fisiología , Humanos , Metotrexato/toxicidad , Fase de Descanso del Ciclo Celular , Células del Estroma/citología , Células del Estroma/ultraestructuraRESUMEN
BACKGROUND: PBSC transplant provides 10 times more T cells than BMT However, the incidence and severity of acute GvHD is similar among recipients of both types of transplants. Studies in mouse models suggest that the similar clinical outcome in BMT and PBSCT is due to differences in the lymphokine profiles. METHODS: PBMC, PBMC from G-CSF mobilized donors (G-PBMC)and BM mononuclear cells (BM-MC) were analyzed by flow cytometry and ELISA to detect gamma-IFN and IL-4 production. Hematoxylin and eosin staining was used to identify morphology and annexin/propidium-iodide was used for apoptosis assays. RESULTS: We show decreased production of gamma-interferon (85%) and IL-4 (60%) in G-PBMC when compared with either PBMC or BM-MCT cells on ex vivo assays. Surprisingly, 85% of fresh G-PBMC is composed of low-density granulocytes (LDG), which undergo apoptosis after 48 h in culture. At this same time, gamma-IFN production from G-PBMC T cell was reverted. In vitro, G-CSF converts granulocytes into LDGs, able to inhibit T-cell function by H2O2 production, and not through immune-deviation towards a Th2-type phenotype. DISCUSSION: We show that the estimated numbers of Th1 and Th2 cells infused in BMT and PBSCT do not differ significantly. These findings are discussed with reference to the relatively low incidence of acute GvHD in PBSCT shown in the literature. We suggest that these results might depend on the high number of granulocytes and progenitors infused. The potential use of granulocytes as immunosupressive short-term therapy is now being investigated by our group using a mouse experimental model.
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Granulocitos/fisiología , Trasplante de Células Madre de Sangre Periférica , Linfocitos T/fisiología , Acetato de Tetradecanoilforbol/análogos & derivados , Anexina A5/análisis , Antígenos CD/análisis , Apoptosis/fisiología , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/fisiología , Trasplante de Médula Ósea , Complejo CD3/análisis , Catalasa/farmacología , Recuento de Células , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos/farmacología , Granulocitos/citología , Granulocitos/efectos de los fármacos , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Humanos , Peróxido de Hidrógeno/metabolismo , Interferón gamma/análisis , Interleucina-4/análisis , Ionomicina/farmacología , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/fisiología , Leucosialina , Prueba de Cultivo Mixto de Linfocitos , Activación Neutrófila/efectos de los fármacos , Activación Neutrófila/fisiología , Sialoglicoproteínas/análisis , Linfocitos T/química , Linfocitos T/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacología , Factores de TiempoRESUMEN
There is concern that modularity in a total hip arthroplasty system increases serum cobalt and chromium ion levels. This study measures the serum cobalt and chromium levels in patients with an Oxford Universal Hip (Corin, Cirencester, United Kingdom), which has a modular sliding mechanism; patients with a similarly manufactured hip with no sliding mechanism; and a control group. Loosening was excluded clinically and radiologically. Arthroplasty patients had statistically higher levels of serum cobalt and chromium than controls, but there was no significant difference in levels between the implanted groups.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Cromo/sangre , Cobalto/sangre , Humanos , Periodo PosoperatorioRESUMEN
Programmed cell death by apoptosis of unnecessary or potentially harmful cells is clearly beneficial to multicellular organisms. Proper functioning of such a program demands that the removal of dying cells proceed without an inflammatory reaction. Phosphatidylserine (PS) is one of the ligands displayed by apoptotic cells that participates in their noninflammatory removal when recognized by neighboring phagocytes. PS ligation induces the release of transforming growth factor-beta (TGF-beta), an antiinflammatory cytokine that mediates the suppression of macrophage-mediated inflammation. In Hydra vulgaris, an organism that stands at the base of metazoan evolution, the selective advantage provided by apoptosis lies in the fact that Hydra can survive recycling apoptotic cells by phagocytosis. In unicellular organisms, it has been proposed that altruistic death benefits clonal populations of yeasts and trypanosomatids. Now we show that advantageous features of the apoptotic process can operate without death as the necessary outcome. Leishmania spp are able to evade the killing activity of phagocytes and establish themselves as obligate intracellular parasites. Amastigotes, responsible for disease propagation, similar to apoptotic cells, inhibit macrophage activity by exposing PS. Exposed PS participates in amastigote internalization. Recognition of this moiety by macrophages induces TGF-beta secretion and IL-10 synthesis, inhibits NO production, and increases susceptibility to intracellular leishmanial growth.
Asunto(s)
Apoptosis , Regulación hacia Abajo/fisiología , Hydra/fisiología , Leishmania/fisiología , Macrófagos/inmunología , Macrófagos/microbiología , AnimalesAsunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Linfocinas/efectos de los fármacos , Linfocitos T/química , Adyuvantes Inmunológicos/farmacología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Linfocinas/sangre , Células TH1/química , Células TH1/efectos de los fármacos , Células Th2/química , Células Th2/efectos de los fármacos , Donantes de TejidosRESUMEN
We determined the outcome of 56 'Oxford' unicompartmental replacements performed for anteromedial osteoarthritis of the knee between 1982 and 1987. Of these, 24 were in patients who had died without revision, one was lost to follow-up and two had been revised. Of the remaining 29 knees, 26 were examined clinically and radiologically, two were only examined clinically and one patient was contacted by telephone. The mean age of the patients was 80.3 years. At a mean follow-up of 11.4 years (10 to 14) the measurements of the knee score, range of movement and degree of deformity were not significantly different from those made one to two years after operation, except that the range of flexion had improved. Comparison of fluoroscopically-controlled radiographs at a similar interval of time showed no change in the appearance of the lateral compartments. The retained articular cartilage continued to function for ten or more years which suggests that anteromedial osteoarthritis may be considered as a focal disorder of the knee. This justifies continued efforts to develop methods of treatment which preserve intact joint structures.