906 resultados para Monocyte subsets


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Objective: Many diseases, including atherosclerosis, involve chronic inflammation. The master transcription factor for inflammation is NF-κB. Inflammatory sites have a low extracellular pH. Our objective was to demonstrate the effect of pH on NF-κB activation and cytokine secretion. Methods: Mouse J774 macrophages or human THP-1 or monocyte-derived macrophages were incubated at pH 7.0–7.4 and inflammatory cytokine secretion and NF-κB activity were measured. Results: A pH of 7.0 greatly decreased pro-inflammatory cytokine secretion (TNF or IL-6) by J774 macrophages, but not THP-1 or human monocyte-derived macrophages. Upon stimulation of mouse macrophages, the levels of IκBα, which inhibits NF-κB, fell but low pH prevented its later increase, which normally restores the baseline activity of NF-κB, even though the levels of mRNA for IκBα were increased. pH 7.0 greatly increased and prolonged NF-κB binding to its consensus promoter sequence, especially the anti-inflammatory p50:p50 homodimers. Human p50 was overexpressed using adenovirus in THP-1 macrophages and monocyte-derived macrophages to see if it would confer pH sensitivity to NF-κB activity in human cells. Overexpression of p50 increased p50:p50 DNA-binding and in THP-1 macrophages inhibited considerably TNF and IL-6 secretion, but there was still no effect of pH on p50:p50 DNA binding or cytokine secretion. Conclusion: A modest decrease in pH can sometimes have marked effects on NF-κB activation and cytokine secretion and might be one reason to explain why mice normally develop less atherosclerosis than do humans.

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Superposed epoch studies have been carried out in order to determine the ionospheric response at mid-latitudes to southward turnings of the interplanetary magnetic field (IMF). This is compared with the geomagnetic response, as seen in the indices K p, AE and Dst. The solar wind, IMF and geomagnetic data used were hourly averages from the years 1967–1989 and thus cover a full 22-year cycle in the solar magnetic field. These data were divided into subsets, determined by the magnitudes of the southward turnings and the concomitant increase in solar wind pressure. The superposed epoch studies were carried out using the time of the southward turning as time zero. The response of the mid-latitude ionosphere is studied by looking at the F-layer critical frequencies, f o F2, from hourly soundings by the Slough ionosonde and their deviation from the monthly median values, δf o F2. For the southward turnings with a change in B z of δB z > 11.5 nT accompanied by a solar wind dynamic pressure P exceeding 5 nPa, the F region critical frequency, f o F2, shows a marked decrease, reaching a minimum value about 20 h after the southward turning. This recovers to pre-event values over the subsequent 24 h, on average. The Dst index shows the classic storm-time decrease to about −60 nT. Four days later, the index has still to fully recover and is at about −25 nT. Both the K p and AE indices show rises before the southward turnings, when the IMF is strongly northward but the solar wind dynamic pressure is enhanced. The average AE index does register a clear isolated pulse (averaging 650 nT for 2 h, compared with a background peak level of near 450 nT at these times) showing enhanced energy deposition at high latitudes in substorms but, like K p, remains somewhat enhanced for several days, even after the average IMF has returned to zero after 1 day. This AE background decays away over several days as the Dst index recovers, indicating that there is some contamination of the currents observed at the AE stations by the continuing enhanced equatorial ring current. For data averaged over all seasons, the critical frequencies are depressed at Slough by 1.3 MHz, which is close to the lower decile of the overall distribution of δf o Fl values. Taking 30-day periods around summer and winter solstice, the largest depression is 1.6 and 1.2 MHz, respectively. This seasonal dependence is confirmed by a similar study for a Southern Hemisphere station, Argentine Island, giving peak depressions of 1.8 MHz and 0.5 MHz for summer and winter. For the subset of turnings where δB z > 11.5 nT and P ≤ 5 nPa, the response of the geomagnetic indices is similar but smaller, while the change in δf o F2 has all but disappeared. This confirms that the energy deposited at high latitudes, which leads to the geomagnetic and ionospheric disturbances following a southward turning of the IMF, increases with the energy density (dynamic pressure) of the solar wind flow. The magnitude of all responses are shown to depend on δB z . At Slough, the peak depression always occurs when Slough rotates into the noon sector. The largest ionospheric response is for southward turnings seen between 15–21 UT.

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As a model for brain inflammation we previously studied transcriptional profiles of tumor necrosis factor-alpha (TNF)treated U373 astroglioma cells. In previous work we were able to demonstrate that the chemokine monocyte chemoattractant protein-1 (MCP-1, SCYA2, CCL2, MCAF) expression in U373 cells was inducible by TNF-alpha treatment. Demonstrably MCP-1 mRNA and protein expression in U373 cells was sustainable over time and at the highest level of all genes analyzed (Schwamborn et al., BMC Genomics 4, 46, 2003). In the hematopoietic system MCP-1 is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural killer cells. In search of further functions in brain inflammation we tested the hypothesis that MCP-1 acts as a chemokine on neural stem cells. Here we report that MCP-1 activates the migration capacity of rat-derived neural stem cells. The migration of stem cells in a Boyden chamber analysis was elevated after stimulation with MCP-1. Time-lapse video microscopy visualized the migration of single stem cells from neurospheres in MCP-1-treated cultures, whereas untreated cultures depicted no migration at all, but showed signs of sprouting. Expression of the MCP-1 receptor CCR2 in neurosphere cultures was verified by RT-PCR and immunofluorescence microscopy. Supernatants from TNF-treated U373 cells also induced migration of neural stem cells.

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Trace element measurements in PM10–2.5, PM2.5–1.0 and PM1.0–0.3 aerosol were performed with 2 h time resolution at kerbside, urban background and rural sites during the ClearfLo winter 2012 campaign in London. The environment-dependent variability of emissions was characterized using the Multilinear Engine implementation of the positive matrix factorization model, conducted on data sets comprising all three sites but segregated by size. Combining the sites enabled separation of sources with high temporal covariance but significant spatial variability. Separation of sizes improved source resolution by preventing sources occurring in only a single size fraction from having too small a contribution for the model to resolve. Anchor profiles were retrieved internally by analysing data subsets, and these profiles were used in the analyses of the complete data sets of all sites for enhanced source apportionment. A total of nine different factors were resolved (notable elements in brackets): in PM10–2.5, brake wear (Cu, Zr, Sb, Ba), other traffic-related (Fe), resuspended dust (Si, Ca), sea/road salt (Cl), aged sea salt (Na, Mg) and industrial (Cr, Ni); in PM2.5–1.0, brake wear, other traffic-related, resuspended dust, sea/road salt, aged sea salt and S-rich (S); and in PM1.0–0.3, traffic-related (Fe, Cu, Zr, Sb, Ba), resuspended dust, sea/road salt, aged sea salt, reacted Cl (Cl), S-rich and solid fuel (K, Pb). Human activities enhance the kerb-to-rural concentration gradients of coarse aged sea salt, typically considered to have a natural source, by 1.7–2.2. These site-dependent concentration differences reflect the effect of local resuspension processes in London. The anthropogenically influenced factors traffic (brake wear and other traffic-related processes), dust and sea/road salt provide further kerb-to-rural concentration enhancements by direct source emissions by a factor of 3.5–12.7. The traffic and dust factors are mainly emitted in PM10–2.5 and show strong diurnal variations with concentrations up to 4 times higher during rush hour than during night-time. Regionally influenced S-rich and solid fuel factors, occurring primarily in PM1.0–0.3, have negligible resuspension influences, and concentrations are similar throughout the day and across the regions.

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Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: −0.4, −0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752.

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The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca(2 +) ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.

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1. Comparative analyses are used to address the key question of what makes a species more prone to extinction by exploring the links between vulnerability and intrinsic species’ traits and/or extrinsic factors. This approach requires comprehensive species data but information is rarely available for all species of interest. As a result comparative analyses often rely on subsets of relatively few species that are assumed to be representative samples of the overall studied group. 2. Our study challenges this assumption and quantifies the taxonomic, spatial, and data type biases associated with the quantity of data available for 5415 mammalian species using the freely available life-history database PanTHERIA. 3. Moreover, we explore how existing biases influence results of comparative analyses of extinction risk by using subsets of data that attempt to correct for detected biases. In particular, we focus on links between four species’ traits commonly linked to vulnerability (distribution range area, adult body mass, population density and gestation length) and conduct univariate and multivariate analyses to understand how biases affect model predictions. 4. Our results show important biases in data availability with c.22% of mammals completely lacking data. Missing data, which appear to be not missing at random, occur frequently in all traits (14–99% of cases missing). Data availability is explained by intrinsic traits, with larger mammals occupying bigger range areas being the best studied. Importantly, we find that existing biases affect the results of comparative analyses by overestimating the risk of extinction and changing which traits are identified as important predictors. 5. Our results raise concerns over our ability to draw general conclusions regarding what makes a species more prone to extinction. Missing data represent a prevalent problem in comparative analyses, and unfortunately, because data are not missing at random, conventional approaches to fill data gaps, are not valid or present important challenges. These results show the importance of making appropriate inferences from comparative analyses by focusing on the subset of species for which data are available. Ultimately, addressing the data bias problem requires greater investment in data collection and dissemination, as well as the development of methodological approaches to effectively correct existing biases.

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Lymphocyte subsets, activation markers and apoptosis were assessed in 20 HIV-exposed noninfected (ENI) children born to HIV-infected women who were or not exposed to antiretroviral (ARV) drugs during pregnancy and early infancy. ENI children and adolescents were aged 6-18 years and they were compared to 25 age-matched healthy non-HIV-exposed children and adolescents (Control). ENI individuals presented lower CD4(+) T cells/mm(3) than Control group (control: 1120.3 vs. ENI: 876.3; t-test, p=0.030). ENI individuals had higher B-cell apoptosis than Control group (Control: 36.6%, ARV exposed: 82.3%, ARV nonexposed: 68.5%; Kruskal-Wallis, p < 0.05), but no statistical difference was noticed between those exposed and not exposed to ARV. Immune activation in CD4(+) T, CD8(+) T and in B cells was comparable in ENI and in Control children and adolescents. Subtle long-term immune alterations might persist among ENI individuals, but the clinical consequences if any are unknown, and these children require continued monitoring.

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Progressive renal failure continues to be a challenge. The use of bone marrow cells represents a means of meeting that challenge. We used lineage-negative (Lin(-)) cells to test the hypothesis that Lin(-) cell treatment decreases renal injury. Syngeneic Fischer 344 rats were divided into four groups: sham ( laparotomy only, untreated); Nx (five-sixth nephrectomy and untreated); NxLC1 (five-sixth nephrectomy and receiving 2 x 10(6) Lin(-) cells on postnephrectomy day 15); and NxLC3 (five-sixth nephrectomy and receiving 2 x 10(6) Lin(-) cells on postnephrectomy days 15, 30, and 45). On postoperative day 16, renal mRNA expression of interleukin (IL)-1 beta, tumor necrosis factor-alpha, and IL-6 was lower in NxLC rats than in Nx rats. On postnephrectomy day 60, NxLC rats presented less proteinuria, glomerulosclerosis, anemia, renal infiltration of immune cells, and protein expression of monocyte chemoattractant protein-1, as well as decreased interstitial area. Immunostaining for proliferating cell nuclear antigen showed that, in comparison with sham rats, Nx rats presented greater cell proliferation, whereas NxLC1 rats and NxLC3 rats presented less cell proliferation than did Nx rats. Protein expression of the cyclin-dependent kinase inhibitor p21 and of vascular endothelial growth factor increased after nephrectomy and decreased after Lin(-) cell treatment. On postnephrectomy day 120, renal function (inulin clearance) was significantly better in Lin(-) cell-treated rats than in untreated rats. Lin(-) cell treatment significantly improved survival. These data suggest that Lin(-) cell treatment protects against chronic renal failure. STEM CELLS 2009; 27: 682-692

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The mechanisms resulting in large daily rainfall events in Northeast Brazil are analyzed using data filtering to exclude periods longer than 30 days. Composites of circulation fields that include all independent events do not reveal any obvious forcing mechanisms as multiple patterns contribute to Northeast Brazil precipitation variability. To isolate coherent patterns, subsets of events are selected based on anomalies that precede the Northeast Brazil precipitation events at different locations. The results indicate that at 10 degrees S, 40 degrees W, the area of lowest annual rainfall in Brazil, precipitation occurs mainly in association with trailing midlatitude synoptic wave trains originating in either hemisphere. Closer to the equator at 5 degrees S, 37.5 degrees W, an additional convection precursor is found to the west, with a spatial structure consistent with that of a Kelvin wave. Although these two sites are located within only several hundred kilometers of each other and the midlatitude patterns that induce precipitation appear to be quite similar, the dates on which large precipitation anomalies occur at each location are almost entirely independent, pointing to separate forcing mechanisms.

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The bees of the Peponapes genus (Eucerini, Apidae) have a Neotropical distribution with the center of species diversity located in Mexico and are specialized in Cucurbita plants. which have many species of economic importance. such as squashes and pumpkins Peponapis fervens is the only species of the genus known from southern South America The Cucurbita species occurring in the same area as P fervens Include four domesticated species (C ficifolia, C maxima maxima, C moschata and C pepo) and one non-domesticated species (Cucurbita maxima andreana) It was suggested that C. in andreana was the original pollen source to P fervens, and this bee expanded its geographical range due to the domestication of Cucurbita The potential geographical areas of these species were determined and compared using ecological niche modeling that was performed with the computational system openModeller and GARP with best subsets algorithm The climatic variables obtained through modeling were compared using Cluster Analysis Results show that the potential areas of domesticated species practically spread all over South America The potential area of P fervens Includes the areas of C m andreana but reaches a larger area, where the domesticated species of Cucurbita also Occur The Cluster Analysis shows a high climatic similarity between P fervens and C. m. andreana Nevertheless. P fervens presents the ability to occupy areas with wider ranges of climatic variables and to exploit resources provided by domesticated species (C) 2009 Elsevier B V All rights reserved

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P>1. Much of the current understanding of ecological systems is based on theory that does not explicitly take into account individual variation within natural populations. However, individuals may show substantial variation in resource use. This variation in turn may be translated into topological properties of networks that depict interactions among individuals and the food resources they consume (individual-resource networks). 2. Different models derived from optimal diet theory (ODT) predict highly distinct patterns of trophic interactions at the individual level that should translate into distinct network topologies. As a consequence, individual-resource networks can be useful tools in revealing the incidence of different patterns of resource use by individuals and suggesting their mechanistic basis. 3. In the present study, using data from several dietary studies, we assembled individual-resource networks of 10 vertebrate species, previously reported to show interindividual diet variation, and used a network-based approach to investigate their structure. 4. We found significant nestedness, but no modularity, in all empirical networks, indicating that (i) these populations are composed of both opportunistic and selective individuals and (ii) the diets of the latter are ordered as predictable subsets of the diets of the more opportunistic individuals. 5. Nested patterns are a common feature of species networks, and our results extend its generality to trophic interactions at the individual level. This pattern is consistent with a recently proposed ODT model, in which individuals show similar rank preferences but differ in their acceptance rate for alternative resources. Our findings therefore suggest a common mechanism underlying interindividual variation in resource use in disparate taxa.

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Many macrophage functions are modulated by fatty acids (FAs), including cytokine release, such as tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is of great interest due to its role in the inflammation process observed in several diseases such as rheumatoid arthritis, atherosclerosis, and obesity. However, the mechanisms by which FA effects occur have not been completely elucidated yet. In this study, we used a mouse monocyte lineage (J774 cells) to evaluate the effect of 50 and 100 mu M of saturated (palmitic and stearic acids), monounsaturated (oleic acid) and polyunsaturated (linoleic acid) FAs on TNF-alpha production. Alterations in gene expression, poly(A) tail length and activation of transcription factors were evaluated. Oleic and linoleic acids, usually known as neutral or pro-inflammatory FA, inhibited LPS-induced TNF-alpha secretion by the cells. Saturated FAs were potent inducers of TNF-alpha expression and secretion under basal and inflammatory conditions (in the presence of LPS). Although the effect of the saturated FA was similar, the mechanism involved in each case seem to be distinct, as palmitic acid increased EGR-1 and CREB binding activity and stearic acid increased mRNA poly(A) tail. These results may contribute to the understanding of the molecular mechanisms by which saturated FAs modulate the inflammatory response and may lead to design of associations of dietary and pharmacological strategies to counteract the pathological effects of TNF-alpha.

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Introduction: A sedentary lifestyle increases the risk of developing cardiovascular disease, obesity, and diabetes. This phenomenon is supported by recent studies suggesting a chronic, low-grade inflammation status. Endotoxin derived from gut flora may be key to the development of inflammation by stimulating the secretion of inflammatory factors. This study aimed to examine plasma inflammatory markers and endotoxin levels in individuals with a sedentary lifestyle and/or in highly trained subjects at rest. Methods: Fourteen male subjects (sedentary lifestyle n = 7; highly trained subjects n = 7) were recruited. Blood samples were collected after an overnight fast (similar to 12 h). The plasmatic endotoxin, plasminogen activator inhibitor type-1 (PAI-1), monocyte chemotactic protein-1 (MCP1), ICAM/CD54, VCAM/CD106 and lipid profile levels were determined. Results: Endotoxinemia was lower in the highly trained subject group relative to the sedentary subjects (p < 0.002). In addition, we observed a positive correlation between endotoxin and PAI-1 (r = 0.85, p < 0.0001), endotoxin and total cholesterol (r = 0.65; p < 0.01), endotoxin and LDL-c (r = 0.55; p < 0.049) and endotoxin and TG levels (r = 0.90; p < 0.0001). The plasma levels of MCP-1, ICAM/CD54 and VCAM/CD106 did not differ. Conclusion: These results indicate that a lifestyle associated with high-intensity and high-volume exercise induces favorable changes in chronic low-grade inflammation markers and may reduce the risk for diseases such as obesity, diabetes and cardiovascular diseases.

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Scavenger or Fc gamma receptors are important for capture and clearance of modified LDL particles by monocytes/macrophages. Uptake via scavenger receptors is not regulated by intracellular levels of cholesterol and in consequence, macrophages develop into foam cells in the arterial intima. The levels of scavenger receptor CD36 are increased in atherosclerotic lesions and there is evidence that some components of oxLDL auto-regulate the expression of this receptor. Fc gamma receptor expression is increased in cardiovascular diseases but it is not known weather their expression is regulated by oxLDL. The biological properties of oxLDLs vary depending on the degree of oxidation. In the present study we investigated the effect of LDL particles showing extensive or low oxidation (HoxLDL and LoxLDL) on the expression of CD36 and Fc gamma RII in a human monocytic cell line (THP-1), differentiated or not to macrophage, and the involvement of PPAR gamma. It was found that both forms of oxLDL are able to increase the expression of CD36 and Fc gamma RII and that this effect is dependent on the degree of oxidation and of the stage of cell differentiation ( monocyte or macrophage). We also showed that the increased expression of Fc gamma RII is dependent on PPAR. whereas that of the CD36 is independent of PPAR gamma. Copyright (c) 2008 S. Karger AG, Basel