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1.
J Allergy Clin Immunol ; 148(1): 139-147.e10, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33766551

RESUMEN

BACKGROUND: Air pollutants are suspected to affect pathological conditions of allergic rhinitis (AR). OBJECTIVES: After detecting Pb (375 µg/kg) in Japanese cedar pollen, the effects of intranasal exposure to Pb on symptoms of AR were investigated. METHODS: Pollen counts, subjective symptoms, and Pb levels in nasal epithelial lining fluid (ELF) were investigated in 44 patients with Japanese cedar pollinosis and 57 controls from preseason to season. Effects of intranasal exposure to Pb on symptoms were confirmed by using a mouse model of AR. RESULTS: Pb levels in ELF from patients were >40% higher than those in ELF from control subjects during the pollen season but not before the pollen season. Pb level in ELF was positively associated with pollen counts for the latest 4 days before visiting a hospital as well as scores of subjective symptoms. Intranasal exposure to Pb exacerbated symptoms in allergic mice, suggesting Pb as an exacerbation factor. Pb levels in ELF and nasal mucosa in Pb-exposed allergic mice were higher than those in Pb-exposed nonallergic mice, despite intranasally challenging the same amount of Pb. Because the increased Pb level in the nasal mucosa of Pb-exposed allergic mice was decreased after washing the nasal cavity, Pb on the surface of but not inside the nasal mucosa may have been a source of increased Pb level in ELF of allergic mice. CONCLUSIONS: Increased nasal Pb level partially derived from pollen could exacerbate subjective symptoms of AR, indicating Pb as a novel hazardous air pollutant for AR.


Asunto(s)
Contaminantes Atmosféricos/inmunología , Alérgenos/inmunología , Plomo/inmunología , Cavidad Nasal/inmunología , Mucosa Nasal/inmunología , Rinitis Alérgica/inmunología , Adulto , Animales , Cryptomeria/inmunología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Líquido del Lavado Nasal/inmunología , Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Estaciones del Año
2.
Artículo en Inglés | MEDLINE | ID: mdl-29621150

RESUMEN

There has been growing concern over the impact of environmental exposure to heavy metals and other trace elements on immunologic functions. This study investigated men's arsenic (As), cadmium (Cd) and lead (Pb) contents in hair samples and their associations with immunological indicators, including white blood cell (WBC), lymphocyte and monocyte counts, and the immunoglobulin (Ig) levels including IgA, IgG and IgE. We recruited 133 men from one antimony trioxide manufacturing plant, two glass manufacturing plants and two plastics manufacturing plants. The mean concentration of Cd [0.16 (SD = 0.03) ug/g] was lower than means of As [0.86 (SD = 0.16) ug/g] and Pb [0.91 (SD = 0.22) ug/g] in hair samples, exerting no relationship with immunologic functions for Cd. The Spearman's correlation analysis showed a positive relationship between monocyte counts and hair Pb levels, but negative relations between As and IgG and between As and IgE. In conclusion, findings from these industry workers suggest that As levels in hair may have a stronger relation with immunologic function than Cd and PB have. Further research is needed to confirm the negative relationship.


Asunto(s)
Arsénico/análisis , Cadmio/análisis , Cabello/química , Plomo/análisis , Metales Pesados/análisis , Metales Pesados/inmunología , Exposición Profesional/efectos adversos , Adulto , Anciano , Arsénico/inmunología , Cadmio/inmunología , Femenino , Humanos , Plomo/inmunología , Masculino , Persona de Mediana Edad , Exposición Profesional/análisis , Taiwán
3.
Am J Rhinol Allergy ; 30(2): e48-52, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26980386

RESUMEN

BACKGROUND: Results of several studies showed that blood lead concentration is positively associated with total immunoglobulin E (IgE) value. However, no study has investigated whether allergic sensitization could be responsible for the association between lead exposure and total IgE value. OBJECTIVE: We investigated whether there was difference in the association between lead exposure and the total IgE value, depending on the presence or absence of Dermatophagoides farinae sensitization. METHODS: We used data obtained from the Korea National Health and Nutrition Examination Survey. Serum levels of heavy metals, such as mercury, cadmium, and lead, were measured. Total and D. farinae specific IgE levels were measured, and the urinary cotinine level was investigated. Information about sex, age, body mass index, and household income were also obtained. We analyzed the association between serum lead and total IgE levels, after adjusting other variables. RESULTS: In an multivariate linear regression analysis, only the serum concentration of lead among the three heavy metals was positively associated with logarithmic transformed total IgE (coefficient [B], 0.026 [95% confidence interval {CI}], 0.008-0.044). When we performed the same analysis on groups divided by allergic D. farinae sensitization status, we found a significant positive association between serum lead and logarithmic transformed total IgE values in subjects with D. farinae sensitization (B, 0.043 [95% CI, 0.014-0.071]) but not in subjects without D. farinae sensitization (B, 0.015 [95% CI, -0.008 to 0.039]). CONCLUSIONS: A positive association between the serum lead and total IgE levels was statistically significant in subjects with D. farinae sensitization, which indicated that the immunologic effects of lead exposure may be greater in people with allergic sensitization.


Asunto(s)
Hipersensibilidad/inmunología , Inmunoglobulina E/inmunología , Plomo/inmunología , Adulto , Animales , Antígenos Dermatofagoides/inmunología , Cotinina/orina , Dermatophagoides farinae , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Inmunización , Inmunoglobulina E/sangre , Plomo/efectos adversos , Plomo/sangre , Masculino , Persona de Mediana Edad , República de Corea
4.
Int J Hyg Environ Health ; 217(2-3): 196-204, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23726529

RESUMEN

Early life lead exposure may alter immune function and predispose a child to develop asthma. In an initial exploration of this hypothesis, we examined the association between blood lead, and serum immunoglobulin E (IgE), eosinophils, and asthma prevalence in a cross-sectional study of 1788 children from the National Health and Nutrition Examination Survey 2005-2006. Geometric mean blood lead, serum IgE, and percent eosinophils were 1.13 µg/dL (95% confidence interval (CI): 1.04, 1.22), 46.3 kU/L (95% CI: 40.3, 53.1), and 2.82 percent (95% CI 2.67, 2.98), respectively. Prevalence of asthma, atopic asthma, and atopy were 11.8% (95% CI: 9.5, 14.2), 8.1% (6.2, 9.9), and 44.4% (40.1, 48.7), respectively. Regression models controlled for season, age, sex, race/ethnicity, education, passive smoke exposure, and body mass index. Based on these models, there was an 11.1% (95% CI: 5.6, 16.9) increase in IgE and a 4.9% (95% CI: 2.3, 7.6) increase in eosinophils per 1 µg/dL increase in blood lead. In independent stratified analyses, lead was found to increase IgE and eosinophils among non-Hispanic whites, but not other children; and stronger associations were observed among children who lived with a smoker vs. not. Lead was not associated with asthma, atopic asthma, or general atopy. This study provides additional evidence of a cross-sectional association between lead with IgE and new evidence for eosinophils. This may be a mechanism for development of downstream allergic disease. The mechanisms that determine ultimate development of allergic disease are currently unknown, but are the focus of ongoing studies.


Asunto(s)
Asma , Eosinófilos/metabolismo , Inmunoglobulina E/sangre , Plomo , Asma/epidemiología , Asma/etiología , Niño , Preescolar , Estudios Transversales , Etnicidad , Femenino , Humanos , Hipersensibilidad Inmediata/epidemiología , Hipersensibilidad Inmediata/etiología , Plomo/sangre , Plomo/inmunología , Masculino , Encuestas Nutricionales , Prevalencia , Contaminación por Humo de Tabaco
5.
J Hazard Mater ; 189(1-2): 255-64, 2011 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-21377791

RESUMEN

Induction of tumor necrosis factor-α (TNF-α) in response to lead (Pb) exposure has been implicated in its immunotoxicity. However, the molecular mechanism by which Pb upregulates the level of TNF-α is wagely known. An attempt was therefore made to elucidate the mechanistic aspect of TNF-α induction, mainly focusing transcriptional and post transcriptional regulation via mitogen activated protein kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic THP-1 cells resulted in significant enhanced production of TNF-α m-RNA and protein secretion. Moreover, the stability of TNF-α m-RNA was also increased as indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb exposed THP-1 was also evident. Specific inhibitor of ERK1/2, PD 98059 caused significant inhibition in production and stability of TNF-α m-RNA. However, SB 203580 partially inhibited production and stability of TNF-α m-RNA. Interestingly, a combined exposure of these two inhibitors completely blocked modulation of TNF-α m-RNA. Data tends to suggest that expression and stability of TNF-α induction due to Pb exposure is mainly regulated through ERK. Briefly, these observations are useful in understanding some mechanistic aspects of proinflammatory and immunotoxicity of Pb, a globally acknowledged key environmental contaminant.


Asunto(s)
Sustancias Peligrosas/farmacología , Plomo/farmacología , Fagocitos/metabolismo , Activación Transcripcional/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Línea Celular , Sustancias Peligrosas/inmunología , Humanos , Plomo/inmunología , Proteína Quinasa 3 Activada por Mitógenos/fisiología , Fagocitos/efectos de los fármacos , Estabilidad del ARN , ARN Mensajero
6.
Environ Res ; 111(1): 119-24, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21094490

RESUMEN

BACKGROUND: Several in vivo and in vitro studies have shown that metal-rich particles may enhance allergic responses to house dust mites and induce an increased release of allergy-related cytokines. OBJECTIVES: The main goal of this analysis is to define the possible association of intrauterine exposure to lead and mercury with the occurrence of skin sensitization to common aeroallergens in early childhood. MATERIAL AND METHODS: The present study refers to a sample of 224 women in the second trimester of pregnancy recruited from Krakow inner city area who had full term pregnancies and whose children underwent skin prick testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord blood and retested in children at age of 5 years. Aeroallergen concentrations in house dust were measured at the age of 3 years. The main health outcome (atopic status) was defined as the positive SPT to at least one common aeroallergen (Der f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis of the association between atopic status of children and exposure to metals, the study considered a set of covariates such as maternal characteristics (age, education, atopy), child's gender, number of older siblings, prenatal (measured via cord blood cotinine) and postnatal environmental tobacco smoke together with exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA adducts. RESULTS AND CONCLUSION: In the binary regression analysis, which controlled for the confounders, the risk ratio (RR) estimate for atopic sensitization was significantly associated with the lead exposure (RR=2.25, 95%CI: 1.21-4.19). In conclusion, the data suggest that even very low-level of prenatal lead exposure may be implicated in enhancing sensitization to common aeroallergens in early childhood.


Asunto(s)
Alérgenos/efectos adversos , Hipersensibilidad/etiología , Intoxicación por Plomo/inmunología , Plomo/inmunología , Efectos Tardíos de la Exposición Prenatal , Adolescente , Adulto , Preescolar , Estudios de Cohortes , Aductos de ADN/sangre , Polvo/inmunología , Femenino , Sangre Fetal/química , Sangre Fetal/inmunología , Humanos , Hipersensibilidad/sangre , Hipersensibilidad/inmunología , Plomo/sangre , Intoxicación por Plomo/sangre , Modelos Logísticos , Masculino , Exposición Materna/efectos adversos , Oportunidad Relativa , Hidrocarburos Policíclicos Aromáticos/sangre , Embarazo , Estudios Prospectivos , Adulto Joven
7.
Environ Toxicol Chem ; 28(2): 402-8, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18811227

RESUMEN

Marine organisms are continuously exposed to heavy metals in their environment. Bivalve mollusks such as the blue mussel Mytilus edulis accumulate high levels of heavy metals effecting cellular homeostasis and functions. Lead (Pb) exposure (2.5 mg/L of lead (II) nitrate for 10 d) and depuration (10 d in clean seawater) experiments were conducted to study its intracellular fate in the gills and digestive gland of M. edulis. For this purpose, an antibody-based detection method for ultrastructural localization and a subcellular fractionation approach for chemical analysis of Pb were used. In addition, effects of Pb on enzyme activities involved in oxyradical scavenging, such as the conjugative enzyme glutathione-S-transferase and the antioxidative enzyme catalase, were determined. The ultrastructural studies showed that Pb was mainly detected in lysosomes of gill epithelial cells and digestive cells. Lead was also detected in cell nuclei and granular hemocytes. Higher metal concentrations were measured by chemical analysis in subcellular fractions of the gills compared to those of the digestive gland. Increased activities of glutathione-S-transferase were found in gills after exposure and remained elevated during the depuration period, whereas glutathione-S-transferase activity remained unaffected in the digestive gland. Catalase activities showed no changes after Pb exposure, neither in the gills nor in the digestive gland. We conclude that gill cells are major sites of uptake and accumulation for dissolved Pb and are involved in sequestration and detoxification of this metal in M. edulis.


Asunto(s)
Anticuerpos/inmunología , Bivalvos/metabolismo , Sistema Digestivo/metabolismo , Branquias/metabolismo , Plomo/metabolismo , Animales , Sistema Digestivo/enzimología , Sistema Digestivo/ultraestructura , Branquias/enzimología , Branquias/ultraestructura , Plomo/inmunología , Microscopía Electrónica
8.
J Agric Food Chem ; 55(13): 4993-8, 2007 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-17547420

RESUMEN

Monoclonal antibodies against lead were generated by immunizing BALB/c mice with lead conjugated to keyhole limpet hemocyanin (KLH) via a bifunctional chelator, S-2-(4-aminobenzyl)diethylenetriamine pentaacetic acid (DTPA). Stable hybridoma cell lines were produced by fusion of murine splenocytes and SP2/0 myeloma cells. One of the hybridomas generated from this fusion (4/7) synthesized and secreted an antibody that bound tightly to Pb2+-DTPA complexes but not to metal-free DTPA. The performance for a competitive inhibition enzyme-linked immunosorbent assay (ELISA) incorporating this antibody was assessed for its sensitivity to changes in pH, ionic strength, and blocking reagents. The cross-reactivities in this ELISA were less than 3% for Fe3+, Cd2+, Hg2+, and Cu2+ and less than 0.3% for Cr3+, Mn2+, Mg2+, In3+, Ag1+, Ni2+, Co2+, Zn2+, Ca2+, Cu1+, and Hg1+. The IC50 value achieved for lead was 2.72 +/- 0.034 microM, showing the detection range of 0.092-87.2 microM and the lowest detection limit of 0.056 +/- 0.005 microM. Recoveries from the analyte-fortified tap water and ultrapure water were in the range of 80-114% . These results indicate that the ELISA could be a convenient analytical tool for monitoring lead residues in drinking water.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Quelantes , Inmunoensayo , Plomo/inmunología , Ácido Pentético/análogos & derivados , Animales , Anticuerpos Monoclonales/biosíntesis , Especificidad de Anticuerpos , Quelantes/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Plomo/análisis , Ratones , Ratones Endogámicos BALB C
9.
Toxicol Appl Pharmacol ; 198(3): 283-90, 2004 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-15276407

RESUMEN

We evaluated in Mexican children environmentally exposed to arsenic and lead monocyte nitric oxide (NO) and superoxide anion production in response to direct activation with interferon-gamma (IFN-gamma) + lipopolysaccharide (LPS). The integrity of Th1-regulated cellular immune response when monocytes were indirectly activated was also evaluated. Most children lived near a primary lead smelter. Lead and arsenic contamination in soil and dust by far exceeded background levels. As levels in water were between 10 and 30 ppb. Most children (93%) had urinary arsenic (AsU) concentrations above 50 microg/l (range 16.75-465.75) and 65% had lead blood levels (PbB) above 10 microg/dl (range 3.47-49.19). Multivariate analyses showed that NO production in monocytes activated indirectly was negatively associated with both PbB and AsU. Superoxide production in directly activated monocytes was negatively associated with AsU but positively associated with PbB. The models including the interaction term for AsU and PbB suggested the possibility of a negative interaction for NO production and a positive interaction for superoxide. There were indications of differential gender-based associations, NO production in indirectly activated monocytes obtained from girls was negatively associated with AsU but not with PbB. Superoxide production was positively associated with PbB in both directly and indirectly activated monocytes from boys but the latter was negatively associated with AsU. These effects are consistent with immune system abnormalities observed in human populations exposed to Pb or As. Further studies in larger populations are required to characterize As and Pb interactions and the mechanism(s) underlying the observed effects.


Asunto(s)
Arsénico/efectos adversos , Contaminantes Ambientales/efectos adversos , Plomo/efectos adversos , Monocitos/efectos de los fármacos , Óxido Nítrico/biosíntesis , Superóxidos/metabolismo , Arsénico/sangre , Arsénico/inmunología , Niño , Estudios Transversales , Contaminantes Ambientales/sangre , Contaminantes Ambientales/inmunología , Femenino , Humanos , Interferón gamma/farmacología , Plomo/sangre , Plomo/inmunología , Lipopolisacáridos/farmacología , Masculino , México , Monocitos/inmunología , Monocitos/metabolismo
10.
Biochemistry ; 42(48): 14173-83, 2003 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-14640685

RESUMEN

The molecular characterization of antibodies directed against metal-chelate complexes will provide important insights into the design and development of radiotherapeutic and radioimaging reagents. In this study, two monoclonal antibodies directed against different metal-chelate complexes were expressed as recombinant Fab fragments. Covalent modification and site-directed mutagenesis were employed to ascertain those residues important in antigen recognition. Antibody 5B2 was raised to a Pb(II)-loaded isothiocyanatobenzyl-diethylenetriamine pentaacetic acid (DTPA)-protein conjugate. The native antibody bound to complexes of Pb(II)-p-aminobenzyl-DTPA with an affinity of 4.6 x 10(-9) M. A monovalent Fab fragment prepared from the native protein and a bivalent recombinant fragment exhibited comparable affinities for the same Pb(II)-chelate complex, approximately 6-fold lower than that of the intact antibody. Covalent modification and molecular modeling predicted that Lys(58) in the heavy chain contacted the Pb(II)-chelate ligand. Mutational analysis supported a role for Lys(58) in ion pair or hydrogen bond formation with the carboxylate groups on the chelate. Antibody E5 was directed toward an isothiocyanatobenzyl-ethylenediamine tetraacetic acid (EDTA)-protein conjugate loaded with ionic Cd(II). The native immunoglobulin recognized Cd(II)-p-aminobenzyl-EDTA with an affinity of 8.2 x 10(-12) M. A proteolytically derived fragment and a bivalent recombinant fragment bound to the same Cd(II)-chelate complex with affinities that were comparable to that of the native antibody. Homology modeling and mutagenesis identified three residues (Trp(52) and His(96) in the heavy chain and Arg(96) in the light chain) that were important for Cd(II)-chelate recognition. His(96) likely mediates a direct ligation to the Cd(II) ion and Trp(52) appears to be involved in hydrophobic stacking with the benzyl moiety of the chelator. Arg(96) appeared to mediate an electrostatic or hydrogen bond to the chelate portion of the complex. These studies demonstrate that antibody recognition of metal-chelate haptens occurs through a limited number of molecular contacts and that these molecular interactions involve both direct ligation between the antibody and the metal ion and interactions between the antibody and the chelator.


Asunto(s)
Aminoácidos/química , Anticuerpos Monoclonales/química , Sitios de Unión de Anticuerpos , Quelantes/química , Metales Pesados/química , Sustitución de Aminoácidos/genética , Aminoácidos/genética , Animales , Anticuerpos Monoclonales/genética , Antígenos/química , Antígenos/inmunología , Sitios de Unión de Anticuerpos/genética , Ácido Edético/química , Ácido Edético/inmunología , Inmunoensayo , Inmunoglobulina G/química , Plomo/química , Plomo/inmunología , Lisina/química , Metales Pesados/inmunología , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Ácido Pentético/química , Ácido Pentético/inmunología , Estructura Terciaria de Proteína/genética , Proteínas Recombinantes/química
11.
Environ Res ; 92(2): 124-8, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12854692

RESUMEN

Serum immunoglobulin (IgG, IgM, and IgE) concentrations of 38 preschool children with blood lead levels > or = 0.48 pmol/L (10 microg/ dL) were examined and compared to 35 preschool children with blood lead levels < or = 0.48 micromol/L. No differences in serum concentrations of IgG, IgM, and IgE in the populations were observed, but IgG, IgM, and IgE of male and female children from the high blood lead level group were compared to those of controls and the results showed that IgG and IgM were significantly lower in the high blood lead level group of females than in the controls, while IgE was significantly higher in the high blood lead level group of females than in the controls (P < 0.05). No correlation between blood lead concentration and serum immunogloblins IgG and IgM was demonstrated, but a statistically significant relationship between IgE and blood lead level was found in this population. These data indicate that the effect of lead on IgG, IgM, and IgE was stronger in females than in males and lead could play a role in this process by stimulating IgE production.


Asunto(s)
Inmunoglobulinas/sangre , Plomo/efectos adversos , Niño , Preescolar , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Plomo/sangre , Plomo/inmunología , Masculino , Factores Sexuales
12.
Toxicology ; 188(2-3): 251-9, 2003 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-12767695

RESUMEN

Lead is a ubiquitous pollutant in the industrial environment, which poses serious threats to human health. In the past 20 years increasing attention has been paid to the effects of lead exposure on health. This toxic metal alters the immune response of animals as well as humans. To study the immunological effects of occupational exposure to lead, we examined lymphocyte proliferation, natural killer (NK) cell cytotoxicity and interferon-gamma production with peripheral blood mononuclear cells (PBMCs) of individuals occupationally exposed to lead. We selected three different groups of individuals exposed to lead: three-wheeler drivers (30), battery workers (34) and silver jewelery makers (20); and unexposed healthy volunteers (30) as control for comparison. Our results indicate that though lymphocyte proliferation to phytohaemagglutinin (PHA) is inhibited in lead exposed individuals as compared with unexposed volunteers, there is no correlation between inhibition of lymphocyte proliferation and blood lead level. NK cell cytotoxicity remains unaffected in individuals exposed to lead as compared with controls. On the other hand, we observed that interferon-gamma (IFN-gamma) was significantly elevated in T cell mitogen, PHA, stimulated PBMCs culture supernatant of lead exposed individuals. We found significant positive correlation between blood lead levels and IFN-gamma produced in culture supernatant on stimulation with PHA. In brief, this study demonstrates that lead can affect the immune response of the occupationally exposed individuals such as three-wheeler drivers, battery reconditioning workers and silver jewelery makers.


Asunto(s)
Células Asesinas Naturales/efectos de los fármacos , Plomo/efectos adversos , Leucocitos Mononucleares/efectos de los fármacos , Linfocitos/efectos de los fármacos , Exposición Profesional/efectos adversos , Pruebas Inmunológicas de Citotoxicidad , Citotoxicidad Inmunológica/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Industria Procesadora y de Extracción , Humanos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Plomo/sangre , Plomo/inmunología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Linfocitos/citología , Linfocitos/inmunología , Masculino , Fitohemaglutininas/farmacología , Emisiones de Vehículos/efectos adversos
13.
Biochemistry ; 42(2): 497-508, 2003 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-12525177

RESUMEN

Detailed equilibrium binding studies were conducted on a monoclonal antibody directed against Pb(II) complexed with a protein conjugate of diethylenetriaminepentaacetic acid (DTPA). Binding curves obtained with DTPA and a cyclohexyl derivative of DTPA in the presence and absence of metal ions were consistent with the anticipated one-site homogeneous binding model. Binding curves obtained with aminobenzyl-DTPA or its complexes with Ca(II), Sr(II), and Ba(II) were highly sigmoidal, characterized by Hill coefficients of 2.3-6.5. Binding curves obtained with the Pb(II) and In(III) complexes of aminobenzyl-DTPA were hyperbolic, but in each case the apparent affinity of the antibody for the chelator-metal complex was higher in the presence of excess chelator than it was in the presence of excess metal ion. In the presence of excess chelator, the equilibrium dissociation constant for the binding of aminobenzyl-DTPA-Pb(II) to the antibody was 9.5 x 10(-)(10) M. Binding curves obtained with the Hg(II) and Cd(II) complexes of aminobenzyl-DTPA were biphasic, indicative of negative cooperativity. Further binding studies demonstrated that aminobenzyl-DTPA-Hg(II) opposed the binding of additional chelator-metal complexes to the antibody more strongly than did aminobenzyl-DTPA-Cd(II). The Fab fragment differed from the intact antibody only in that the apparent affinity of the Fab was generally lower for a given chelator-metal complex. These data are interpreted in terms of a model in which (i) aminobenzyl-DTPA and its complexes bind both to the antigen binding site and to multiple charged sites on the surface of the compact immunoglobulin; and (ii) the bound, highly charged ligands interact in a complicated fashion through the apolar core of the folded antibody.


Asunto(s)
Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/metabolismo , Sitios de Unión de Anticuerpos , Fragmentos Fab de Inmunoglobulinas/química , Fragmentos Fab de Inmunoglobulinas/metabolismo , Ácido Pentético/análogos & derivados , Regulación Alostérica , Secuencia de Aminoácidos , Animales , Unión Competitiva , Cadmio/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Haptenos/administración & dosificación , Haptenos/inmunología , Hemocianinas/administración & dosificación , Hemocianinas/inmunología , Hibridomas , Inyecciones Intravenosas , Plomo/administración & dosificación , Plomo/inmunología , Compuestos de Mercurio/inmunología , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Ácido Pentético/administración & dosificación , Ácido Pentético/inmunología
14.
Environ Sci Technol ; 36(5): 1042-7, 2002 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-11917989

RESUMEN

Lead concentrations were determined by a fluorescence polarization immunoassay (FPIA) method that uses polyclonal antibodies raised against the lead(II) chelate of ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA). The technique is based on competition for a fixed concentration of antibody binding sites between Pb-EDTA, formed by treating the sample with excess EDTA, and a fixed concentration of a fluorescent analogue of the Pb-EDTA complex. The objective was to correlate results obtained by FPIA with those produced by conventional atomic spectroscopy analysis of soils, solid waste leachates (produced by the Toxicity Characteristic Leachate Procedure; TCLP), airborne dust, and drinking water. Linear regression analysis of FPIA results for 138 soil samples containing 0-3094 ppm Pb(II) by flame atomic absorption spectroscopy and 40 TCLP extracts containing 0-668 ppm Pb(II) by inductively coupled plasma atomic emission spectroscopy produced correlation coefficients (r2) of 0.96 and 0.93, respectively. Pilot studies of mineral acid extracts of airborne dust trapped on fiberglass filters and of two sources of drinking water demonstrated the feasibility of also measuring lead in these matrixes by FPIA. The limit of detection under conditions that minimized sample dilution was approximately 1 ppb, and cross reactivity with 15 nontarget metals was below 0.5% in all cases. The methods are simple to perform and are amenable to field testing and mobile laboratory use, allowing timely and cost-effective characterization of suspected sources of lead contamination.


Asunto(s)
Quelantes/química , Ácido Edético/química , Monitoreo del Ambiente/métodos , Plomo/análisis , Contaminantes Atmosféricos/análisis , Animales , Anticuerpos/análisis , Formación de Anticuerpos , Inmunoensayo/métodos , Plomo/inmunología , Conejos , Contaminantes del Agua/análisis , Abastecimiento de Agua
15.
Toxicol Appl Pharmacol ; 177(3): 219-31, 2001 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-11749121

RESUMEN

T cells are believed to be critical functional targets of Pb immunotoxicity. In this study, low concentrations of lead (i.e., as low as 0.1 microM approximately 2 microg/dl) were found to markedly enhance the allogeneic mixed lymphocyte reaction-an assay of CD4(+) T cell responsiveness. Cell cycle analysis of cells recovered from allogeneic mixed lymphocyte cultures revealed that Pb stimulated a substantial increase in the proportion of cycling alloreactive CD4(+) T cells. The enhanced alloproliferative response was characterized by an increased population of lymphoblasts expressing heightened cell surface expression of CD4 (i.e., CD4(high) cells). Successive rounds of cell division were monitored using the cell division dye 5- (and 6)-carboxyfluorecein diacetate succinimyl ester and it was determined that the CD4(high) subpopulation comprised the expanding alloreactive T cells, which ultimately took on the phenotype of memory/effector T cells (i.e., CD44(high), CD45RB(low), CD69(high), and CD162(high)). Enhancement of T cell proliferation by lead was selective for responsiveness to alloantigen, as lead had no effect on T cell proliferation induced by mitogens or superantigen, processes that unlike alloreactivity are not dependent on antigen presentation. Collectively, these data suggest that Pb enhances alloantigen-specific T cell proliferation through an indirect mechanism involving altered antigen processing/presentation, resulting in marked clonal expansion or repertoire expansion of alloreactive T cell clones. Consistent with this suggestion was the finding that a single exposure to Pb during alloantigen priming elicited a population of CD4(+) T cells that was hyperresponsive to further alloantigen stimulation and neither lead dependent nor lead responsive.


Asunto(s)
Linfocitos T CD4-Positivos/efectos de los fármacos , Isoantígenos/inmunología , Plomo/toxicidad , Animales , Antígenos CD/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Recuento de Células , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , Femenino , Citometría de Flujo , Memoria Inmunológica/efectos de los fármacos , Memoria Inmunológica/inmunología , Inmunofenotipificación , Plomo/inmunología , Prueba de Cultivo Mixto de Linfocitos , Ratones , Ratones Endogámicos , Mitógenos/inmunología , Mitógenos/farmacología , Superantígenos/inmunología , Superantígenos/farmacología
16.
Toxicology ; 169(1): 67-80, 2001 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11696410

RESUMEN

Heavy metal environmental pollutants increase susceptibility of affected individuals to bacterial and viral infections, but the mechanisms responsible for this effect are not known. We established cellular in vitro systems to identify molecular targets for the action of heavy metal ions. We used two model systems to determine the effects of heavy metal ions on antigen-induced T lymphocyte responses. The first system was representative of primary antigen responses and utilized CD4(+) primary T lymphocytes derived from DO.11.10 T cell receptor transgenic mice. The second system represented a memory T cell phenotype and utilized the CD4(+) T helper 1 clone, pGL2. We measured the effects of the four heavy metals cadmium, lead, mercury, and vanadium on cytokine and proliferation responses by purified CD4(+) T cell to antigenic stimulation. Cytokine responses were differentially affected by lead and vanadium at concentrations that did not affect T cell proliferation in response to antigen. We also determined whether the metal ions induced apoptotic cell death. Mercury induced apoptosis at concentrations as low as 0.5 microM, whereas cadmium required a concentration of 100 microM. Lead (maximal concentration tested was 200 microM) and vanadium (100 microM) did not induce apoptosis. The results suggested that the different heavy metal ions differentially affected antigen-stimulated responses in T helper cells. These in vitro systems can now be applied to test whether heavy metal ions alter antigen-induced T cell signal transduction pathways in CD4(+) T helper cells.


Asunto(s)
Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Metales Pesados/inmunología , Contaminantes Atmosféricos/inmunología , Contaminantes Atmosféricos/toxicidad , Animales , Células Presentadoras de Antígenos/inmunología , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Cadmio/inmunología , Cadmio/toxicidad , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Interleucina-1/inmunología , Plomo/inmunología , Plomo/toxicidad , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Linfocinas/análisis , Linfocinas/biosíntesis , Masculino , Mercurio/inmunología , Mercurio/toxicidad , Metales Pesados/toxicidad , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Vanadio/inmunología , Vanadio/toxicidad
18.
Alergia (Méx.) ; 40(4): 95-7, jul.-ago. 1993.
Artículo en Español | LILACS | ID: lil-134920

RESUMEN

La evaluación del estado inmunológico en trabajadores expuestos en razón de su trabajo al plomo fue el motivo de este estudio realizado a 14 trabajadores, los que fueron comparados con otros no expuestos, de edad y sexos similares (grupo control).La concentración media de plomo en sangre de la población expuesta fue de 46.9+- 2.3 ng/dl. No hubo diferencias significativas en las concentraciones del suero IgC, IgA e IgM entre las poblaciones estudiadas. Se comprobó la correlación entre la concentración de plomo en la sangre y los niveles de inmunoglobulinas G. Encontramos alteraciones significativas en las pruebas de formación de rosetas (R A y R E)


Asunto(s)
Humanos , Masculino , Adulto , Inmunoglobulinas/inmunología , Plomo/inmunología , Técnicas Inmunológicas/instrumentación , Inmunoglobulina A/análisis , Inmunoglobulina A/inmunología , Inmunoglobulina G/análisis , Inmunoglobulina G/inmunología , Inmunoglobulina M/análisis , Inmunoglobulina M/inmunología , Inmunoglobulinas/análisis , Plomo/sangre , Medicina del Trabajo
19.
Alergia (Méx.) ; 40(2): 33-6, mar.-abr. 1993. tab
Artículo en Español | LILACS | ID: lil-134893

RESUMEN

Se evaluó el estado inmunológico de 14 trabajadores expuestos por razones de su ocupación al plomo, los sujetos estudiados se compararon con otros no expuestos, de edad y sexo similares (grupo testigo). La concentración medida de plomo en la sangre de la población expuesta fue 46,9 ñ 2,3 µg/dl. No hubo diferencias significativas en las concentraciones del suero IgG, IgA e IgM entre las poblaciones estudiadas. Se comprobó la correlación entre la concentración de plomo en sangre y el inmunoglobulinas G


Asunto(s)
Humanos , Masculino , Adulto , Exposición a Riesgos Ambientales/efectos adversos , Inmunoglobulinas/inmunología , Plomo/inmunología , Exposición a Riesgos Ambientales/análisis , Inmunoglobulinas/análisis , Plomo/sangre , Medicina del Trabajo
20.
Rev Alerg Mex (1987) ; 38(2): 69-72, 1991.
Artículo en Español | MEDLINE | ID: mdl-1754824

RESUMEN

The evaluation of immunological conditions of 14 workers occupationally exposed to lead, and the comparison of these results with those of a non-exposed control group, with similar age and sex, were the aims of this study. It was determined the mean values of lead in blood. In exposed workers it was 46.9 micrograms/dl; while in the control group it was 10.9 micrograms/dl. Levels of immunoglobulin decreasing while increasing lead concentration in blood were found in those exposed. It was also found a significant lessening in the formation of rosette in relation to the control group.


Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Inmunoglobulinas/análisis , Plomo/farmacología , Exposición Profesional , Adulto , Depresión Química , Humanos , Plomo/inmunología , Persona de Mediana Edad , Formación de Roseta , Linfocitos T/inmunología
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