Papers by ANTONIO SOTO VEGA
Geologica Acta, Jan 11, 2006
The sedimentary rocks intercalated in volcanic and metavolcanic sections of Mayarí-Baracoa and Si... more The sedimentary rocks intercalated in volcanic and metavolcanic sections of Mayarí-Baracoa and Sierra del Purial Mountains (Eastern Cuba), yielded Cretaceous through Danian microfossils. In the Mayarí Mountains the Téneme Fm consists of basalts and hyaloclastites with minor intercalations of well-bedded foliated limestone and shaly limestone that in the type area contain a Turonian or early Coniacian planktonic foraminifera assemblage. In the Morel area (Moa-Baracoa massif), back-arc pillow basalts with ribbon cherts include a late Turonian or Coniacian limestone bed intercalated with interbedded organic-rich calcareous shales near the top. The upper part of the Coniacian (?)-Campanian Santo Domingo Fm crops out west of Moa and it consists of finegrained well-bedded volcaniclastic rocks with two intercalated lenses of coarse-grained impure biocalcirudites to biocalcarenites. These rocks yielded a mixed penecontemporaneous planktonic and benthonic microfossil assemblage attributed to the lower part of the late Campanian (Globotruncanita calcarata Zone). At Sierra del Purial, crystalline limestones embedded within the metavulcano-sedimentary Río Baracoa section (Purial metamorphic complex) yielded Campanian microfossils. The Maastrichtian Yaguaneque (=Cañas) limestones crop out extensively in both Mayarí-Baracoa and Purial Mountains. All the formations previously mentioned unconformably overlie and tectonically intermingle with the late Maastrichtian-early Danian clastic rocks of the Mícara and La Picota Fms. Our new dates demonstrate that in the Greater Antilles the PIA (Primitive Island Arc-tholeiite) recorded by the Téneme Fm would be Late Cretaceous in age in opposition to the Lower Cretaceous age proposed for the PIA basalts. The protolith of the Purial metamorphic complex is probably Maastrichtian-early Danian, but certainly Campanian and older in age. This fact suggests that the metamorphism that affected the Purial rocks took place probably in the late Maastrichtian and was coeval with the detachment, exhumation and emplacement of mafic-ultramafic thrust-sheet bodies. This event recorded in Eastern Cuba/Western Hispaniola and Guatemala might have been related to the insertion of thick oceanic ridges into the subduction zone.
Geologica Acta, Jan 11, 2006
The Téneme Formation is located in the Mayarí-Cristal ophiolitic massif and represents one of the... more The Téneme Formation is located in the Mayarí-Cristal ophiolitic massif and represents one of the three Cretaceous volcanic Formations established in northeastern Cuba. Téneme volcanics are cut by small bodies of 89.70 ± 0.50 Ma quarz-diorite rocks (Río Grande intrusive), and are overthrusted by serpentinized ultramafics. Téneme volcanic rocks are mainly basalts, basaltic andesites, andesites, and minor dacites, and their geochemical signature varies between low-Ti island arc tholeiites (IAT) with boninitic affinity (TiO 2 < 0.4 %; high field strength elements << N-type MORB) and typical oceanic arc tholeiites (TiO 2 = 0.5-0.8 %). Basaltic rocks exhibit low light REE/Yb ratios (La/Yb < 5), typical of intraoceanic arcs and are comparable to Maimón Formation in Dominican Republic (IAT, pre Albian) and Puerto Rican lavas of volcanic phase I (island arc tholeiites, Aptian to Early Albian). The mantle wedge signature of the Téneme Formation indicates a highly depleted MORB-type mantle source, without any contribution of E-MORB or OIB components. Our results suggest that Téneme volcanism represents a primitive oceanic island arc environment. If the Late Cretaceous age (Turonian or early Coniacian) proposed for Téneme Formation is correct, our results indicate that the Cretaceous volcanic rocks of eastern Cuba and the Dominican Republic are not segments of a single arc system, and that in Late Cretaceous (Albian-Campanian) Caribbean island arc development is not represented only by calc-alkaline (CA) volcanic rocks as has been suggested in previous works. Geochemistry. Volcanic rocks. Primitive-island arc. Téneme Formation. Cuba.
PLoS ONE, 2014
CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neu... more CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neutrophils and to endothelial cells. Allergen-specific immunotherapy is widely used to treat allergic diseases, and the molecular mechanisms underlying this therapy are poorly understood. The present work was undertaken to analyze A) the in vitro effect of allergens and immunotherapy on cell-surface CD66b expression of neutrophils from patients with allergic asthma and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b expression of neutrophils from nasal lavage fluid during the spring season. Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid as a general marker of neutrophil activation. Results: CD66b cell-surface expression is upregulated in vitro in response to allergens, and significantly reduced by immunotherapy (p,0.001). Myeloperoxidase activity in nasal lavage fluid was also significantly reduced by immunotherapy, as were the neutrophil cell-surface expression of CD66b and myeloperoxidase (p,0.001). Interestingly, CD66b expression was higher in neutrophils from nasal lavage fluid than those from peripheral blood, and immunotherapy reduced the number of CD66 + MPO + cells in nasal lavage fluid. Thus, immunotherapy positive effects might, at least in part, be mediated by the negative regulation of the CD66b and myeloperoxidase activity in human neutrophils.
Pediatric Allergy and Immunology, 2013
Background: Allergen-specific immunotherapy (IT) is widely used to treat allergic diseases. The m... more Background: Allergen-specific immunotherapy (IT) is widely used to treat allergic diseases. The molecular mechanisms have not been clarified yet completely. The present work was undertaken to analyze the effect of IT in the activation of NF-jB. Methods: Neutrophils from 15 pollen-allergic IT-treated patients, 10 untreated pollenallergic patients, and 10 healthy donors were in vitro stimulated with LPS. NF-jB activation (p65/p52) was measured in their nuclear extracts by enzyme-linked immunosorbent assay (ELISA). IjBa phosphorylation, NF-jB-repressing factor (NRF) activation, and thromboxane A 2 (TXA 2) and Interleukin-8 (IL-8) release were measured by ELISA. Results: There was a positive correlation between the score of symptoms and NF-jB activation in human neutrophils. IT significantly decreased NF-jB activation levels in neutrophils compared with neutrophils from untreated patients. IjBa phosphorylation and NRF activation levels were, respectively, significantly lower and higher in neutrophils from IT-treated patients than from untreated patients. IL-8 and TXA 2 release were significantly lower in neutrophils from IT-treated patients than from untreated patients. Conclusions: IT positive effects are at least in part mediated by the negative regulation of NF-jB activation in human neutrophils. These observations represent a novel view of neutrophils as possible cell target to treat IgE-dependent diseases through NF-jB downmodulation.
Journal of Molecular Endocrinology, 2007
Angiotensin II (Ang II) highly stimulates superoxide anion production by neutrophils. The G-prote... more Angiotensin II (Ang II) highly stimulates superoxide anion production by neutrophils. The G-protein Rac2 modulates the activity of NADPH oxidase in response to various stimuli. Here, we describe that Ang II induced both Rac2 translocation from the cytosol to the plasma membrane and Rac2 GTP-binding activity. Furthermore, Clostridium difficile toxin A, an inhibitor of the Rho-GTPases family Rho, Rac and Cdc42, prevented Ang II-elicited production, phosphorylation of the mitogen-activated protein kinases (MAPKs) p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2, and Rac2 activation. Rac2 GTPase inhibition by C. difficile toxin A was accompanied by a robust reduction of the cytosolic Ca2+ elevation induced by Ang II in human neutrophils. Furthermore, SB203580 and PD098059 act as inhibitors of p38MAPK and ERK1/2 respectively, wortmannin, an inhibitor of phosphatidylinositol-3-kinase, and cyclosporin A, a calcineurin inhibitor, hindered both transloc...
Journal of Leukocyte Biology, 2004
It has been demonstrated that neutrophils are responsible for the release of large amounts of the... more It has been demonstrated that neutrophils are responsible for the release of large amounts of the inflammatory chemokine interleukin-8 (IL-8), associated with inflammation. To further define the mechanisms implicated, we have analyzed the response of human neutrophils from allergic patients to specific antigens or challenge with anti-immunoglobulin (Ig)E antibodies. Neutrophils showed a dose- and time-dependent production of IL-8. The release of the cytokine was parallel to expression of IL-8 mRNA analyzed by the polymerase chain reaction. This expression was transient—it occurred after 3 h of anti-IgE treatment and was maintained for 18 h. Trifluoperazine, EGTA, reduced nicotinamide adenine dinucleotide phosphate-oxidase inhibitors, and reactive oxygen species (ROS) scavengers inhibited IL-8 production, indicating a critical dependence of calcium and oxidative stress. Moreover, an inhibitory effect of cyclosporin A, an immunosuppressor that inhibits calcineurin activity, on IL-8 re...
Journal of Leukocyte Biology, 2004
This report focuses on the modulatory role of endogenous H2O2 on lipopolysaccharide (LPS)/interfe... more This report focuses on the modulatory role of endogenous H2O2 on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced inducible nitric oxide synthase (NOS2) gene expression in rat peritoneal macrophages. Exogenously added H2O2 was initially found to inhibit the synthesis of NOS2, which prompted us to assess the effect of the activity of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) as H2O2-forming enzymes on NOS2 gene expression. In the presence of their substrates, tyramine for MAO and benzylamine for SSAO, intracellular synthesis of H2O2 took place with concomitant inhibition of LPS/IFN-γ-induced NOS2 protein synthesis, as detected by Western blotting, flow cytometry, and immunofluorescence microscopy analyses. Pargyline and semicarbazide, specific inhibitors of MAO and SSAO, respectively, canceled this negative effect of MAO substrates on NOS2 expression. In the presence of Fe2+ and Cu2+ ions, inhibition of NOS2 expression was enhanced, suggesting the ...
Journal of Leukocyte Biology, 2006
Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 ... more Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 isoform is responsible for the increased PG release, taking place under inflammatory conditions, and also, is thought to be involved in allergic and inflammatory diseases. In the present work, we demonstrate that COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies and by antigens in human neutrophils from allergic patients. This induction was detected at mRNA and protein levels and was accompanied by a concomitant PGE2 and thromboxane A2 release. We also show evidence that inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2-aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone, completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting that this process is mediated by reactive oxygen species (ROS) derived from NADPH oxidase activity. Moreover, the mitogen-activated protein kin...
The Journal of Immunology, 2007
The production of eosinophil cationic protein (ECP) in IgE-mediated diseases has been associated ... more The production of eosinophil cationic protein (ECP) in IgE-mediated diseases has been associated mainly with eosinophils, although no IgE-dependent ECP release has been observed in these cells. Because there is increasing evidence of neutrophil participation in allergic processes, we have examined whether human neutrophils from allergic patients were able to produce ECP by an IgE-dependent mechanism. After challenge with specific Ags to which the patients were sensitized, ECP release was detected in the culture medium. Furthermore, intracellular protein was detected by flow cytometry, immunofluorescence staining, and Western blotting. Expression at both mRNA and de novo protein synthesis were detected, respectively, by RT-PCR and radiolabeling with 35S. Ag effect was mimicked by cell treatment with anti-IgE Abs or Abs against FcεRI and galectin-3 (FcεRI>galectin-3), but not against FcεRII. These observations represent a novel view of neutrophils as possible source of ECP in IgE-d...
Journal of Cell Science, 2007
NFAT (nuclear factors of activated T cells) proteins constitute a family of transcription factors... more NFAT (nuclear factors of activated T cells) proteins constitute a family of transcription factors involved in mediating signal transduction. The presence of NFAT isoforms has been described in all cell types of the immune system, with the exception of neutrophils. In the present work we report for the first time the expression in human neutrophils of NFAT2 mRNA and protein. We also report that specific antigens were able to promote NFAT2 protein translocation to the nucleus, an effect that was mimicked by the treatment of neutrophils with anti-immunoglobulin E (anti-IgE) or anti-Fcϵ-receptor antibodies. Antigens, anti-IgE and anti-FcϵRs also increased Ca2+ release and the intracellular activity of calcineurin, which was able to interact physically with NFAT2, in parallel to eliciting an enhanced NFAT2 DNA-binding activity. In addition, specific chemical inhibitors of the NFAT pathway, such as cyclosporin A and VIVIT peptide, abolished antigen and anti-IgE-induced cyclooxygenase-2 (C...
Journal of Biological Chemistry, 2004
International Archives of Allergy and Immunology, 2003
Background: The presence of the three forms of IgE receptor – the heterotrimeric high-affinity re... more Background: The presence of the three forms of IgE receptor – the heterotrimeric high-affinity receptor for IgE (FcΕRI), the low-affinity receptor for IgE (FcΕRII/CD23) and the Mac-2/IgE-binding protein (ΕBP) – has been demonstrated on human neutrophils. We have previously shown that specific allergens are able to activate functional responses by neutrophils from allergic patients sensitized to those allergens. Neutrophils are present at the sites of allergic inflammation. The primary (azurophilic) granules of neutrophils contain a variety of enzymes, such as elastase, that might potentiate inflammation. It is not known whether specific allergens are able to elicit elastase release by neutrophils from allergic patients. In addition, we attempted to evaluate the relationship between neutrophil degranulation and lung function of the patients, measured as FEV1. Methods: Neutrophils were challenged in vitro with the specific allergens that produced clinical symptoms in asthmatic patient...
FEBS Letters, 2004
In the present study, we have examined the potential ability of 5 0-AMP-activated protein kinase ... more In the present study, we have examined the potential ability of 5 0-AMP-activated protein kinase (AMPK) to modulate NADPH oxidase activity in human neutrophils. AMPK activated with either 5 0-aminoimidazole-4-carboxamide ribonucleoside (AICAR) or with 5 0-AMP significantly attenuated both phorbol 12-myristate 13-acetate (PMA) and formyl methionyl leucyl phenylalanine-stimulated superoxide anion ðO À 2 Þ release by human neutrophils, consistently with a reduced translocation to the cell membrane and phosphorylation of a cytosolic component of NADPH oxidase, namely p47 phox. AMPK was found to be present in human neutrophils and to become phosphorylated in response to either AICAR or other stimulators of its enzyme activity. Furthermore, AICAR also strongly reduced PMA-dependent H 2 O 2 release, and induced the phosphorylation of c-jun N-terminal kinase 1 (p46), p38 mitogenactivated protein kinase and extracellular signal-regulated kinase. Present data demonstrate for the first time that the activation of AMPK, in states of low cellular energy charge (such as under high levels of 5 0-AMP) or other signals, could be a factor contributing to reduce the host defense mechanisms.
European Journal of Immunology, 2006
European Journal of Immunology, 2005
Clinical Immunology, 2011
Blood, 2003
Neutrophils are mobilized to the vascular wall during vessel inflammation. Published data are con... more Neutrophils are mobilized to the vascular wall during vessel inflammation. Published data are conflicting on phagocytic nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activation during the hypertensive state, and the capacity of angiotensin II (Ang II) to modulate the intracellular redox status has not been analyzed in neutrophils. We here describe that Ang II highly stimulates endogenous and extracellular O2- production in these cells, consistent with the translocation to the cell membrane of the cytosolic components of NADPH oxidase, p47phox, and p67phox. The Ang II–dependent O2- production was suppressed by specific inhibitors of AT1 receptors, of the p38MAPK and ERK1/2 pathways, and of flavin oxidases. Furthermore, Ang II induced a robust phosphorylation of p38MAPK, ERK1/2, and JNK1/2 (particularly JNK2), which was hindered by inhibitors of NADPH oxidase, tyrosine kinases, and ROS scavengers. Ang II increased cytosolic Ca2+ levels—released mainly from calcium stores...
Atherosclerosis, 2004
Hyperhomocysteinaemia has recently been recognized as a risk factor of cardiovascular disease. Ho... more Hyperhomocysteinaemia has recently been recognized as a risk factor of cardiovascular disease. However, the action mechanisms of homocysteine (Hcy) are not well understood. Given that Hcy may be involved in the recruitment of monocytes and neutrophils to the vascular wall, we have investigated the role of Hcy in essential functions of human neutrophils. We show that Hcy increased superoxide anion (O 2 •−) release by neutrophils to the extracellular medium, and that this effect was inhibited by superoxide dismutase and diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase activity. The enzyme from rat peritoneal macrophages displayed a similar response. These effects were accompanied by a time-dependent increased translocation of p47 phox and p67 phox subunits of NADPH oxidase to the plasma membrane. We also show that Hcy increased intracellular H 2 O 2 production by neutrophils, that Hcy enhanced the activation and phosphorylation of mitogen-activated protein kinases (MAPKs), specifically p38-MAPK and ERK1/2, and that the migration of neutrophils was increased by Hcy. Present results are the first evidence that Hcy enhances the oxidative stress of neutrophils, and underscore the potential role of phagocytic cells in vascular wall injury through O 2 •− release in hyperhomocysteinaemia conditions.
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Papers by ANTONIO SOTO VEGA