RESUMEN
Particulate matter with a diameter ≤2.5â µm (PM2.5) poses a substantial global challenge, with a growing recognition of pathogens contributing to diseases associated with exposure to PM2.5 Recent studies have focused on PM2.5, which impairs the immune cells in response to microbial infections and potentially contributes to the development of severe diseases in the respiratory tract. Accordingly, changes in the respiratory immune function and microecology mediated by PM2.5 are important factors that enhance the risk of microbial pathogenesis. These factors have garnered significant interest. In this review, we summarise recent studies on the potential mechanisms involved in PM2.5-mediated immune system disruption and exacerbation of microbial pathogenesis in the respiratory tract. We also discuss crucial areas for future research to address the gaps in our understanding and develop effective strategies to combat the adverse health effects of PM2.5.
Asunto(s)
Interacciones Huésped-Patógeno , Material Particulado , Infecciones del Sistema Respiratorio , Material Particulado/efectos adversos , Material Particulado/inmunología , Humanos , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/microbiología , Animales , Exposición por Inhalación/efectos adversos , Contaminantes Atmosféricos/efectos adversos , Tamaño de la Partícula , Factores de Riesgo , Sistema Respiratorio/microbiología , Sistema Respiratorio/inmunología , Medición de RiesgoAsunto(s)
Hipersensibilidad , Exposición Profesional , Material Particulado , Humanos , Exposición Profesional/efectos adversos , Material Particulado/efectos adversos , Material Particulado/inmunología , Hipersensibilidad/epidemiología , Hipersensibilidad/inmunología , Hipersensibilidad/etiología , Masculino , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología , Enfermedades Profesionales/inmunología , Adulto , FemeninoRESUMEN
Intrauterine exposure to particulate matter (PM) has been associated with an increased risk of asthma development, which may differ by the age of asthma onset, sex, and pollutant concentration. To investigate the pulmonary effects of in utero exposure to concentrated urban ambient particles (CAPs) in response to house dust mite (HDM) sensitization in juvenile mice. Mice were exposed to CAPs (600 µg/m3 PM2.5) during the gestational period. Twenty-two-day postnatal mice were sensitized with HDM (100 µg, intranasally, 3 times per week). Airway responsiveness (AHR), serum immunoglobulin, and lung inflammation were assessed after 43 days of the postnatal period. Female (n = 47) and male (n = 43) mice were divided into four groups as follows: (1) FA: not exposed to CAPs; (2) CAPs: exposed to CAPs; (3) HDM: sensitized to HDM; and (4) CAPs+HDM: exposed to CAPs and HDM-sensitized. PM2.5 exposure did not worsen lung hyperresponsiveness or allergic inflammation in sensitized animals. The levels of the lung cytokines IL-4, TNF-α, and IL-2 were differentially altered in male and female animals. Males presented hyporesponsiveness and increased lung macrophagic inflammation. There were no epigenetic changes in the IL-4 gene. In conclusion, intrauterine exposure ambient PM2.5 did not worsened allergic pulmonary susceptibility but affected the pulmonary immune profile and lung function, which differed by sex.
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Pulmón/inmunología , Exposición Materna/efectos adversos , Material Particulado/toxicidad , Efectos Tardíos de la Exposición Prenatal/inmunología , Animales , Citocinas/inmunología , Femenino , Inmunoglobulinas/sangre , Inmunoglobulinas/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Material Particulado/inmunología , Neumonía/inmunología , Embarazo , Pyroglyphidae/inmunología , Hipersensibilidad Respiratoria/inmunologíaRESUMEN
Diesel exhaust particles (DEPs), traffic-related air pollutants, are considered environmental factors adversely affecting allergic diseases. However, the immunological basis for the adjuvant effects of DEP in allergic rhinitis (AR) remains unclear. Therefore, this study aimed to investigate the effect of DEP exposure on AR using a mouse model. BALB/c mice sensitized to house dust mite (HDM) were intranasally challenged with HDM in the presence and absence of DEP. Allergic symptom scores, serum total and HDM-specific immunoglobulins (Igs), eosinophil infiltration in the nasal mucosa, cytological profiles in bronchoalveolar lavage fluid (BALF), and cytokine levels in the nasal mucosa and spleen cell culture were analyzed. Mice co-exposed to HDM and DEP showed increased allergic symptom scores compared with mice exposed to HDM alone. Reduced total IgE and HDM-specific IgE and IgG1 levels, decreased eosinophil infiltration in the nasal mucosa, and increased proportion of neutrophils in BALF were found in mice co-exposed to HDM and DEP. Interleukin (IL)-17A level was found to be increased in the nasal mucosa of the co-exposure group compared with that in the HDM-exposed group. The levels of IL-4, IL-13, interferon-γ, IL-25, IL-33, and TSLP expression showed no difference between the groups with and without DEP treatment. Increased expression of IL-17A in the nasal mucosa may contribute to DEP-mediated exacerbation of AR in HDM-sensitized murine AR model.
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Alérgenos/inmunología , Interleucina-17/inmunología , Mucosa Nasal/inmunología , Material Particulado/inmunología , Pyroglyphidae/inmunología , Rinitis Alérgica/inmunología , Contaminantes Atmosféricos/inmunología , Animales , Asma/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/inmunología , Modelos Animales de Enfermedad , Femenino , Pulmón/inmunología , Ratones , Ratones Endogámicos BALB C , Hipersensibilidad Respiratoria/inmunologíaRESUMEN
Epidemiological studies have suggested that fine particulate matter (PM2.5) and asthma have been independently associated with pulmonary fibrosis but rarely studied together. Furthermore, it is unknown whether airway fibrosis in asthma is more attributable to water-soluble ions of PM2.5. Our current study was to explore the potential mechanism of PM2.5 and water-soluble components on airway fibrosis in ovalbumin (OVA)-sensitized asthmatic rats. Rats were intratracheally instilled with PM2.5 and water-soluble components every 3 days for 4 times or 8 times. Histopathological examination demonstrated that lung inflammatory and airway fibrosis were induced after PM2.5 and water-soluble components exposure. Meanwhile, PM2.5, in particular water-soluble extracts, increased expression of collagen 1 (COL-1), connective tissue growth factor (CTGF), interleukin-6 (IL-6), transforming growth factor-ß1 (TGF-ß1), Smad family member 3 (Smad3), and p-Smad3, whereas decreased secretion of heme oxygenase-1 (HO-1). However, pretreating asthmatic rats with SB432542, the inhibitor of TGF-ß1, and SIS3 HCl, the antagonist of Smad3, both reversed the activation of airway fibrosis induced by water-soluble extracts. Therefore, TGF-ß1/Smad3 signaling pathway may be responsible for the pathological process of airway fibrosis in asthmatic rats following PM2.5 and water-soluble components exposure.
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Pulmón/inmunología , Material Particulado/inmunología , Fibrosis Pulmonar/inmunología , Transducción de Señal/inmunología , Proteína smad3/inmunología , Factor de Crecimiento Transformador beta1/inmunología , Animales , Asma/inmunología , Modelos Animales de Enfermedad , Masculino , Ovalbúmina/inmunología , Ratas , Ratas Sprague-Dawley , AguaRESUMEN
The lung mucosa functions as a principal barrier between the body and inhaled environmental irritants and pathogens. Precise and targeted surveillance mechanisms are required at this lung-environment interface to maintain homeostasis and preserve gas exchange. This is performed by the innate immune system, a germline-encoded system that regulates initial responses to foreign irritants and pathogens. Environmental pollutants, such as particulate matter (PM), ozone (O3), and other products of combustion (NO2, SO3, etc.), both stimulate and disrupt the function of the innate immune system of the lung, leading to the potential for pathologic consequences. PURPOSE OF REVIEW: The purpose of this review is to explore recent discoveries and investigations into the role of the innate immune system in responding to environmental exposures. This focuses on mechanisms by which the normal function of the innate immune system is modified by environmental agents leading to disruptions in respiratory function. RECENT FINDINGS: This is a narrative review of mechanisms of pulmonary innate immunity and the impact of environmental exposures on these responses. Recent findings highlighted in this review are categorized by specific components of innate immunity including epithelial function, macrophages, pattern recognition receptors, and the microbiome. Overall, the review supports broad impacts of environmental exposures to alterations to normal innate immune functions and has important implications for incidence and exacerbations of lung disease. The innate immune system plays a critical role in maintaining pulmonary homeostasis in response to inhaled air pollutants. As many of these agents are unable to be mitigated, understanding their mechanistic impact is critical to develop future interventions to limit their pathologic consequences.
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Contaminantes Atmosféricos , Inmunidad Innata/inmunología , Enfermedades Pulmonares , Mucosa Respiratoria/inmunología , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/inmunología , Humanos , Pulmón/inmunología , Pulmón/fisiopatología , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/fisiopatología , Ozono/efectos adversos , Ozono/inmunología , Material Particulado/efectos adversos , Material Particulado/inmunología , Mucosa Respiratoria/fisiopatologíaRESUMEN
Recently, a continuous increase in environmental pollution has been observed. Despite wide-scale efforts to reduce air pollutant emissions, the problem is still relevant. Exposure to elevated levels of airborne particles increased the incidence of respiratory diseases. PM10 constitute the largest fraction of air pollutants, containing particles with a diameter of less than 10 µm, metals, pollens, mineral dust and remnant material from anthropogenic activity. The natural airway defensive mechanisms against inhaled material, such as mucus layer, ciliary clearance and macrophage phagocytic activity, may be insufficient for proper respiratory function. The epithelium layer can be disrupted by ongoing oxidative stress and inflammatory processes induced by exposure to large amounts of inhaled particles as well as promote the development and exacerbation of obstructive lung diseases. This review draws attention to the current state of knowledge about the physical features of PM10 and its impact on airway epithelial cells, and obstructive pulmonary diseases.
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Asma/inmunología , Inmunidad Innata/inmunología , Inflamación/inmunología , Estrés Oxidativo/inmunología , Material Particulado/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Mucosa Respiratoria/inmunología , Contaminantes Atmosféricos , Contaminación del Aire , Contaminación del Aire Interior , Asma/metabolismo , Asma/fisiopatología , Progresión de la Enfermedad , Células Epiteliales/metabolismo , Humanos , Inflamación/metabolismo , Moléculas de Patrón Molecular Asociado a Patógenos , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Receptores de Reconocimiento de Patrones/inmunología , Receptores de Reconocimiento de Patrones/metabolismo , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/fisiopatologíaRESUMEN
BACKGROUND: Previous studies have related sulfur dioxide (SO2) exposure to asthma exacerbations. We utilized the University of Pittsburgh Asthma Institute registry to study associations of asthma exacerbations between 2 geographically distinct populations of adults with asthma. OBJECTIVE: Our objective was to examine whether asthma symptoms worsened following a significant fire event that destroyed pollution control equipment at the largest coke works in the United States. METHODS: Two groups of patients with asthma, namely, those residing within 10 miles of the coke works fire (the proximal group [n = 39]) and those residing beyond that range (the control group [n = 44]), were geocoded by residential address. Concentrations of ambient air SO2 were generated by using local University of Pittsburgh Asthma Institute registry air monitoring data. Factory emissions were also evaluated. Data from a patient historical acute exposure survey and in-person follow-up data were evaluated. Inferential statistics were used to compare the groups. RESULTS: In the immediate postfire period (6-8 weeks), the level of emissions of SO2 from the factory emissions increased to 25 times more than the typical level. Following the pollution control breach, the proximal cohort self-reported an increase in medication use (risk ratio = 1.76; 95% CI = 1.1-2.8; P < .01) and more exacerbations. In a small subset of the follow-up cohort of those who completed the acute exposure survey only, asthma control metrics improved. CONCLUSIONS: Real-world exposure to a marked increase in ambient levels of SO2 from a pollution control breach was associated with worsened asthma control in patients proximal to the event, with the worsened control improving following repair of the controls. Improved spatial resolution of air pollutant measurements would enable better examination of exposures and subsequent health impacts.
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Contaminantes Atmosféricos/inmunología , Contaminación del Aire/efectos adversos , Asma/inmunología , Exposición a Riesgos Ambientales/efectos adversos , Estudios de Cohortes , Coque , Contaminación Ambiental/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Material Particulado/inmunología , Dióxido de Azufre/inmunologíaRESUMEN
BACKGROUND: Mast cells play an important role in allergic responses and persistently exposure to environmental fine particulate matter (PM2.5) exacerbates allergic diseases,but the details remained elucidative. OBJECTIVES: To investigate the effect of PM2.5 on IgE-mediated mast cell responses through an IgE-mediated mouse model and mast cell activation. METHODS: The ß-hexosaminidase release and a BALB/c model of passive cutaneous anaphylaxis (PCA) was used to test IgE-mediated mast cells activation in vitro and in vivo. RNA-Seq technique was conducted to study the gene expression profile. Reactive oxygen species (ROS) production was measured by flow-cytometry. RT-PCR,WB and ELISA were performed to examine targeting molecules expression. RESULTS: PM2.5 facilitated IgE-mediated degranulation and increased cytokines expression in mast cells. Meanwhile, the Evan's blue extravasation as well as serum cytokines in mice was increased after treatment with PM2.5. Furthermore, PM2.5 treatment dramatically increased the expression of Gadd45b which is an oxidative stress molecule that directly activates down-stream pathway, such as MEKK4/JNK. PM2.5 treatment activated MEKK4, JNK1/2 but not ERK1/2 and p38. Meanwhile, Knockdown of Gadd45b significantly attenuated PM2.5-mediated JNK1/2 activation and expression of cytokines. In addition, a JNK1/2-specific inhibitor SP600125 blocked IgE-mediated mast cell activation and cytokine release in PCA model mice. Moreover, PM2.5 treatment increased the ROS level and ROS inhibitor dramatically blocked the PM2.5-induced ROS production and reversed the PM2.5-mediated gene expression in the mitochondrial respiratory chain. CONCLUSIONS: PM2.5 regulates ROS production through Gadd45b/MEKK4/JNK pathway, facilitating IgE-mediated mast cell activation.
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Degranulación de la Célula/inmunología , Dermatitis Alérgica por Contacto/inmunología , Mastocitos/inmunología , Material Particulado/efectos adversos , Piel/patología , Animales , Antracenos/administración & dosificación , Antígenos de Diferenciación/metabolismo , Degranulación de la Célula/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Dermatitis Alérgica por Contacto/patología , Modelos Animales de Enfermedad , Transporte de Electrón/efectos de los fármacos , Transporte de Electrón/inmunología , Humanos , Inmunoglobulina E/administración & dosificación , Inmunoglobulina E/inmunología , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Mastocitos/citología , Mastocitos/metabolismo , Ratones , Mitocondrias/metabolismo , Material Particulado/inmunología , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Anafilaxis Cutánea Pasiva/inmunología , RNA-Seq , Ratas , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Piel/citología , Piel/inmunologíaAsunto(s)
Antígenos de Plantas/metabolismo , Toma de Decisiones Clínicas/métodos , Material Particulado/metabolismo , Polen/metabolismo , Rinitis Alérgica Estacional/diagnóstico , Adulto , Alérgenos/inmunología , Antígenos de Plantas/inmunología , Fagales , Femenino , Humanos , Masculino , Región Mediterránea/epidemiología , Material Particulado/inmunología , Pinales , Poaceae , Polen/inmunología , Rinitis Alérgica Estacional/epidemiología , Estaciones del AñoRESUMEN
Despite numerous reports that ambient particulate matter is a key determinant for human health, toxicity data produced based on physicochemical properties of particulate matters is very lack, suggesting lack of scientific evidence for regulation. In this study, we sampled inhalable particulate matters (PM10) in northern Seoul, Korea. PM10 showed atypical- and fiber-type particles with the average size and the surface charge of 1,598.1 ± 128.7 nm and -27.5 ± 2.8, respectively, and various toxic elements were detected in the water extract. On day 90 after the first pulmonary exposure, total cell number dose-dependently increased in the lungs of both sexes of mice. PM10 induced Th1-dominant immune response with pathological changes in both sexes of mice. Meanwhile, composition of total cells and expression of proteins which functions in cell-to-cell communication showed different trends between sexes. Following, male and female mice were mated to identify effects of PM10 to the next generation. PM10 remained in the lung of dams until day 21 after birth, and the levels of IgA and IgE increased in the blood of dams exposed to the maximum dose compared to control. In addition, the interval between births of fetuses, the number of offspring, the neonatal survival rate (day 4 after birth) and the sex ratio seemed to be affected at the maximum dose, and particularly, all offspring from one dam were stillborn. In addition, expression of HIF-1α protein increased in the lung tissue of dams exposed to PM10, and level of hypoxia-related proteins was notably enhanced in PM10-exposed bronchial epithelial cells compared to control. Taken together, we suggest that inhaled PM10 may induce Th1-shifting immune response in the lung, and that it may affect reproduction (fetus development) by causing lung hypoxia. Additionally, we propose that further study is needed to identify particle-size-dependent effects on development of the next generation.
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Contaminantes Atmosféricos/toxicidad , Desarrollo Fetal/efectos de los fármacos , Desarrollo Fetal/inmunología , Inmunidad/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/inmunología , Material Particulado/toxicidad , Contaminantes Atmosféricos/inmunología , Animales , Femenino , Humanos , Masculino , Ratones , Modelos Animales , Material Particulado/inmunología , República de CoreaRESUMEN
PM2.5 causes abnormal immune response and asthma in animals. In this study, a Balb/c mouse animal model was exposed to PM2.5 to induce asthma. Lactobacillus paracasei HB89 was fed at the same time, in order to observe whether L. paracasei HB89 mitigates respiratory tract allergies stimulated by PM2.5. The results showed that PM2.5 stimulated a significant increase in white blood cells and immunoglobulin (IgE) in OVA-induced allergic Balb/c mice, and IgE in the blood further triggered the release of histamine in the lung immune cells. This not only increased overall immune cell counts, but the lymphocyte counts also increased significantly, resulting in significant inhibitions of cytokines INF-r and TGF-ß, and induction of IL-4, IL-5, IL-13 and IL-17a. After feeding with HB89, apart from the absence of observable changes in body weight, the total white blood cell count in the animal blood and IgE response were also be reduced; the proliferation of immune cells in the lungs caused by PM2.5 was slowed down; and histamine and cytokines INF-r and TGF-ß were secreted in large quantities, but IL- 4, IL-5, IL-13, IL-17a were inhibited, which effectively reduced the possibility of asthma induction.
Asunto(s)
Asma/dietoterapia , Citocinas/metabolismo , Inmunoglobulina E/sangre , Lacticaseibacillus paracasei/fisiología , Material Particulado/inmunología , Animales , Asma/inducido químicamente , Asma/inmunología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Histamina/metabolismo , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Material Particulado/efectos adversos , Resultado del TratamientoRESUMEN
Background: It is widely acknowledged that food sensitization is related to atopic dermatitis in infants and young children. Objective: To investigate the association of aeroallergen sensitization with increased rates and severity of atopic dermatitis in school children. Methods: We enrolled 576 children (mean age, 9.4 ± 1.8 years) from six elementary schools. Atopic dermatitis was diagnosed by questionnaires, and severity was rated by physical examinations graded by using the Scoring Atopic Dermatitis (SCORAD) index. Skin-prick tests to 22 common allergens (6 aeroallergens and 16 food allergens) were conducted. Logistic and linear regression analyses were performed by using two models: model I adjusted for age, sex, and body mass index z score; and model II adjusted for all model I factors plus asthma and allergic rhinitis. Results: We diagnosed atopic dermatitis in 22.4% (n = 129) of the children, sensitization to foods in 48.3% (n = 278), and sensitization to aeroallergens in 11.3% (n = 65). A total of 26.2% of the children (n = 149) had mild and 6.5% had moderate-to-severe symptoms and signs of atopic dermatitis (n = 37). Atopic dermatitis was associated with sensitization to aeroallergens and eosinophilia (model I), but this risk was no longer significant after additional adjustment for current allergic status (model II). However, the relationship of the total SCORAD score with aeroallergen sensitization and eosinophilia was significant in model I and model II. Conclusion: The severity of atopic dermatitis correlated with the extent of allergic sensitization and eosinophilia. Analysis of our results suggests that more sensitization to dust mites and eosinophilia are related to increased rates and high severity scores of atopic dermatitis.
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Asma/diagnóstico , Dermatitis Atópica/diagnóstico , Eosinofilia/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Alérgenos/inmunología , Asma/epidemiología , Niño , Dermatitis Atópica/epidemiología , Eosinofilia/epidemiología , Femenino , Hipersensibilidad a los Alimentos/epidemiología , Humanos , Inmunización , Inmunoglobulina E/metabolismo , Masculino , Material Particulado/inmunología , Riesgo , Índice de Severidad de la Enfermedad , Pruebas CutáneasRESUMEN
Environmental pollution is one of the most serious challenges to health in the modern world. Pollutants alter immune responses and can provoke immunotoxicity. In this Review, we summarize the major environmental pollutants that are attracting wide-ranging concern and the molecular basis underlying their effects on the immune system. Xenobiotic receptors, including the aryl hydrocarbon receptor (AHR), sense and respond to a subset of environmental pollutants by activating the expression of detoxification enzymes to protect the body. However, chronic activation of the AHR leads to immunotoxicity. KEAP1-NRF2 is another important system that protects the body against environmental pollutants. KEAP1 is a sensor protein that detects environmental pollutants, leading to activation of the transcription factor NRF2. NRF2 protects the body from immunotoxicity by inducing the expression of genes involved in detoxification, antioxidant and anti-inflammatory activities. Intervening in these sensor-response systems could protect the body from the devastating immunotoxicity that can be induced by environmental pollutants.
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Contaminantes Ambientales/efectos adversos , Contaminación Ambiental/efectos adversos , Inmunidad , Animales , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/química , Contaminantes Ambientales/inmunología , Predisposición Genética a la Enfermedad , Humanos , Hipersensibilidad/etiología , Hipersensibilidad/metabolismo , Hipersensibilidad/prevención & control , Hipersensibilidad/terapia , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Inmunización , Inactivación Metabólica , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Metales/efectos adversos , Metales/química , Metales/inmunología , Células Mieloides/inmunología , Células Mieloides/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Especificidad de Órganos/inmunología , Material Particulado/efectos adversos , Material Particulado/química , Material Particulado/inmunología , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Hidrocarburos Policíclicos Aromáticos/química , Polimorfismo Genético , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
Air pollution, especially that initiated by particulate matter (PM), has been implicated as a risk factor for several inflammatory diseases. Previously, it was reported that PM enhances immune responses. PM includes the tar fraction that contains polycyclic aromatic hydrocarbons (PAHs), which produce adverse health effects in exposed individuals. However, the influence of the tar fraction (as a component of PM) on splenocytes is not fully understood. The aim of this study was to determine the effects of the tar fraction extracted from PM collected from the atmosphere in Fukuoka, Japan, on mouse splenocytes. ICR mice were administered tar (1 or 5 µg/mouse) intratracheally 4 times at 2-week intervals, and splenocytes from the tar-treated mice were extracted and examined. The parameters determined were proliferation, cytokine concentrations and transcription factors activation. Following tar treatment, splenocyte proliferation increased relative to controls. Concanavalin A (ConA)-induced interleukin (IL)-2 formation and ConA- or lipopolysaccharide (LPS)-induced interferon-γ production were elevated in splenocytes from tar-exposed mice. However, the production of tumor necrosis factor-α and IL-6 induced by LPS was not markedly changed following tar treatment. Further, nuclear factor of activated T cells, but not nuclear factor-κB, was enhanced in splenocytes of tar-exposed mice. Data indicate that tar-activated splenocytes and PM-bound PAHs might contribute to T cell activation in the spleen.
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Contaminantes Atmosféricos/inmunología , Polvo/inmunología , Material Particulado/inmunología , Hidrocarburos Policíclicos Aromáticos/inmunología , Bazo/efectos de los fármacos , Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Animales , Japón , Masculino , Ratones , Ratones Endogámicos ICR , Material Particulado/efectos adversos , Hidrocarburos Policíclicos Aromáticos/administración & dosificación , ArenaRESUMEN
Humans have always been in contact with natural airborne particles from many sources including biologic particulate matter (PM) which can exhibit allergenic properties. With industrialization, anthropogenic and combustion-derived particles have become a major fraction. Currently, an ever-growing number of diverse and innovative materials containing engineered nanoparticles (NPs) are being developed with great expectations in technology and medicine. Nanomaterials have entered everyday products including cosmetics, textiles, electronics, sports equipment, as well as food, and food packaging. As part of natural evolution humans have adapted to the exposure to particulate matter, aiming to protect the individual's integrity and health. At the respiratory barrier, complications can arise, when allergic sensitization and pulmonary diseases occur in response to particle exposure. Particulate matter in the form of plant pollen, dust mites feces, animal dander, but also aerosols arising from industrial processes in occupational settings including diverse mixtures thereof can exert such effects. This review article gives an overview of the allergic immune response and addresses specifically the mechanisms of particulates in the context of allergic sensitization, effector function and therapy. In regard of the first theme (i), an overview on exposure to particulates and the functionalities of the relevant immune cells involved in allergic sensitization as well as their interactions in innate and adaptive responses are described. As relevant for human disease, we aim to outline (ii) the potential effector mechanisms that lead to the aggravation of an ongoing immune deviation (such as asthma, chronic obstructive pulmonary disease, etc.) by inhaled particulates, including NPs. Even though adverse effects can be exerted by (nano)particles, leading to allergic sensitization, and the exacerbation of allergic symptoms, promising potential has been shown for their use in (iii) therapeutic approaches of allergic disease, for example as adjuvants. Hence, allergen-specific immunotherapy (AIT) is introduced and the role of adjuvants such as alum as well as the current understanding of their mechanisms of action is reviewed. Finally, future prospects of nanomedicines in allergy treatment are described, which involve modern platform technologies combining immunomodulatory effects at several (immuno-)functional levels.
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Alérgenos/inmunología , Hipersensibilidad/etiología , Hipersensibilidad/inmunología , Material Particulado/efectos adversos , Material Particulado/inmunología , HumanosRESUMEN
Polarization of immune cells is commonly observed in host responses associated with microbial immunity, inflammation, tumorigenesis, and tissue repair and fibrosis. In this process, immune cells adopt distinct programs and perform specialized functions in response to specific signals. Accumulating evidence indicates that inhalation of micro- and nano-sized particulates activates barrier immune programs in the lung in a time- and context-dependent manner, including type 1 and type 2 inflammation, and T helper (Th) 17 cell, regulatory T cell (Treg), innate lymphoid cell (ILC), and myeloid-derived suppressor cell (MDSC) responses, which highlight the polarization of several major immune cell types. These responses facilitate the pulmonary clearance and repair under physiological conditions. When exposure persists and overwhelms the clearance capacity, they foster the chronic progression of inflammation and development of progressive disease conditions, such as fibrosis and cancer. The pulmonary response to insoluble particulates thus represents a distinctive disease process wherein non-infectious, persistent exposures stimulate the polarization of immune cells to orchestrate dynamic inflammatory and immune reactions, leading to pulmonary and pleural chronic inflammation, fibrosis, and malignancy. Despite large variations in particles and their associated disease outcomes, the early response to inhaled particles often follows a common path. The initial reactions entail a barrier immune response dominated by type 1 inflammation that features active phagocytosis by M1 macrophages and recruitment of neutrophils, both of which are fueled by Th1 and proinflammatory cytokines. Acute inflammation is immediately followed by resolution and tissue repair mediated through specialized pro-resolving mediators (SPMs) and type 2 cytokines and cells including M2 macrophages and Th2 lymphocytes. As many particles and fibers cannot be digested by phagocytes, resolution is often extended and incomplete, and type 2 inflammation becomes heightened, which promotes interstitial fibrosis, granuloma formation, and tumorigenesis. Recent studies also reveal the involvement of Th17-, Treg-, ILC-, and MDSC-mediated responses in the pathogenesis caused by inhaled particulates. This review synopsizes the progress in understanding the interplay between inhaled particles and the pulmonary immune functions in disease pathogenesis, with focus on particle-induced polarization of immune cells and its role in the development of chronic inflammation, fibrosis, and cancer in the lung.
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Pulmón/inmunología , Pulmón/patología , Material Particulado/efectos adversos , Material Particulado/inmunología , Animales , Citocinas/inmunología , Células Dendríticas/inmunología , Humanos , Tolerancia Inmunológica , Inmunidad Celular , Inflamación/inmunología , Inflamación/patología , Inhalación , Linfocitos/inmunología , Macrófagos/inmunología , Células Supresoras de Origen Mieloide/inmunología , Transducción de Señal/inmunología , Subgrupos de Linfocitos T/inmunologíaRESUMEN
Asthma, the most common chronic respiratory disease in children, affects numerous people worldwide. Accumulating evidence suggests that exposure to high levels of particulate matter (PM), either acutely or chronically, is associated with the exacerbation and incidence of pediatric asthma. However, the detailed pathogenic mechanisms by which PM contributes to the incidence of asthma remain largely unknown. In this short review, we summarize studies of relationships between PM and pediatric asthma and recent advances on the fundamental mechanisms of PM-related asthma, with emphases on cell death regulation and immune system responses. We further discuss the inadequacy of current studies and give a perspective on the prevention strategies for pediatric asthma.
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Contaminantes Atmosféricos/efectos adversos , Alérgenos/efectos adversos , Asma/inmunología , Exposición a Riesgos Ambientales/efectos adversos , Material Particulado/efectos adversos , Inmunidad Adaptativa/genética , Contaminantes Atmosféricos/inmunología , Asma/epidemiología , Asma/genética , Asma/prevención & control , Niño , Predisposición Genética a la Enfermedad , Humanos , Inmunidad Innata/genética , Inmunidad Mucosa/genética , Incidencia , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/patología , Material Particulado/inmunología , Muerte Celular Regulada/inmunología , Mucosa Respiratoria/citología , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/patología , Brote de los SíntomasRESUMEN
Pathological signaling in the lung induced by particulate matter (PM) air pollution partially overlaps with that provoked by COVID-19, the pandemic disease caused by infection with the novel coronavirus SARS-CoV-2. Metformin is capable of suppressing one of the molecular triggers of the proinflammatory and prothrombotic processes of urban PM air pollution, namely the mitochondrial ROS/Ca2+ release-activated Ca2+ channels (CRAC)/IL-6 cascade. Given the linkage between mitochondrial functionality, ion channels, and inflamm-aging, the ability of metformin to target mitochondrial electron transport and prevent ROS/CRAC-mediated IL-6 release might illuminate new therapeutic avenues to quell the raging of the cytokine and thrombotic-like storms that are the leading causes of COVID-19 morbidity and mortality in older people. The incorporation of infection rates, severity and lethality of SARS-CoV-2 infections as new outcomes of metformin usage in elderly populations at risk of developing severe COVID-19, together with the assessment of bronchial/serological titers of inflammatory cytokines and D-dimers, could provide a novel mechanistic basis for the consideration of metformin as a therapeutic strategy against the inflammatory and thrombotic states underlying the gerolavic traits of SARS-CoV-2 infection.