RESUMEN
Glutamate (Glu) is the major excitatory transmitter in the nervous system. Impairment of its vesicular release by ß-amyloid (Aß) oligomers is thought to participate in pathological processes leading to Alzheimer's disease. However, it remains unclear whether soluble Aß42 oligomers affect intravesicular amounts of Glu or their release in the brain, or both. Measurements made in this work on single Glu varicosities with an amperometric nanowire Glu biosensor revealed that soluble Aß42 oligomers first caused a dramatic increase in vesicular Glu storage and stimulation-induced release, accompanied by a high level of parallel spontaneous exocytosis, ultimately resulting in the depletion of intravesicular Glu content and greatly reduced release. Molecular biology tools and mouse models of Aß amyloidosis have further established that the transient hyperexcitation observed during the primary pathological stage is mediated by an altered behavior of VGLUT1 responsible for transporting Glu into synaptic vesicles. Thereafter, an overexpression of Vps10p-tail-interactor-1a, a protein that maintains spontaneous release of neurotransmitters by selective interaction with t-SNAREs, resulted in a depletion of intravesicular Glu content, triggering advanced-stage neuronal malfunction. These findings are expected to open perspectives for remediating Aß42-induced neuronal hyperactivity and neuronal degeneration.
Asunto(s)
Enfermedad de Alzheimer , Ácido Glutámico , Ratones , Animales , Ácido Glutámico/metabolismo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Neuronas/metabolismo , Encéfalo/metabolismo , Fragmentos de Péptidos/metabolismoRESUMEN
ATP plays a crucial role in cell energy supply, so the quantification of intracellular ATP levels is particularly important for understanding many physio-pathological processes. The intracellular quantification of this non-electroactive molecule can be realized using aptamer-modified nanoelectrodes, but is hindered by the limited quantity of modification and electroactive tags on the nanosized electrodes. Herein, we developed a simple but effective electrochemical signal amplification strategy for intracellular ATP detection, which replaces the regular ATP aptamer-linked ferrocene monomer with a polymer, thus greatly magnifying the amounts of electrochemical reporters linked to one chain of the aptamer and enhancing the signals. This ferrocene polymer-ATP aptamer was further immobilized onto Au nanowire electrodes (SiC@C@Au NWEs) to achieve accurate quantification of intracellular ATP in single cells, presenting high electrochemical signal output and high specificity. This work not only provides a powerful tool for quantifying intracellular ATP but also offers a simple and versatile strategy for electrochemical signal amplification in the detection of broader non-electroactive molecules involved in different kinds of intracellular physiological processes.
Asunto(s)
Adenosina Trifosfato , Aptámeros de Nucleótidos , Técnicas Biosensibles , Técnicas Electroquímicas , Compuestos Ferrosos , Oro , Metalocenos , Adenosina Trifosfato/análisis , Aptámeros de Nucleótidos/química , Humanos , Oro/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Metalocenos/química , Compuestos Ferrosos/química , Técnicas Biosensibles/métodos , Electrodos , Polímeros/química , Nanocables/química , Límite de Detección , Células HeLaRESUMEN
The first examples of alkali metal selenite sulfates, namely, Na8(SeO3)(SO4)3 (1), Na2(H2SeO3)(SO4) (2), and K4(H2SeO3)(HSO4)2(SO4) (3), were successfully synthesized by hydrothermal reactions. Their structures display three different zero-dimensional configurations composed of isolated sulfate tetrahedra and selenite groups separated by alkali metals. Na8(SeO3)(SO4)3 (1) features a noncentrosymmetric structure, while Na2(H2SeO3)(SO4) (2) and K4(H2SeO3)(HSO4)2(SO4) (3) are centrosymmetric. Powder second-harmonic-generation measurements revealed that Na8(SeO3)(SO4)3 (1) shows a phase-matchable SHG intensity about 1.2 times that of KDP. UV-vis-NIR diffuse reflectance spectroscopic analysis indicated that Na8(SeO3)(SO4)3 (1) has a short UV cutoff edge and a large optical band gap, which makes it a possible UV nonlinear optical material. Theoretical calculations revealed that the birefringence of Na8(SeO3)(SO4)3 (1) is 0.041 at 532 nm, which is suitable for phase-matching condition. This work provides a good experimental foundation for the exploration of new UV nonlinear crystals in an alkali metal selenite sulfate system.
RESUMEN
The glutathione (GSH) system is one of the most powerful intracellular antioxidant systems for the elimination of reactive oxygen species (ROS) and maintaining cellular redox homeostasis. However, the rapid kinetics information (at the millisecond to the second level) during the dynamic antioxidation process of the GSH system remains unclear. As such, we specifically developed a novel dual-wire nanosensor (DWNS) that can selectively and synchronously measure the levels of GSH and ROS with high temporal resolution, and applied it to monitor the transient ROS generation as well as the rapid antioxidation process of the GSH system in individual cancer cells. These measurements revealed that the glutathione peroxidase (GPx) in the GSH system is rapidly initiated against ROS burst in a sub-second time scale, but the elimination process is short-lived, ending after a few seconds, while some ROS are still present in the cells. This study is expected to open new perspectives for understanding the GSH antioxidant system and studying some redox imbalance-related physiological.
Asunto(s)
Antioxidantes , Estrés Oxidativo , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno , Glutatión/metabolismo , Oxidación-ReducciónRESUMEN
Interfacing biological tissues with electronic sensors offers the exciting opportunity to accurately investigate multiple biological processes. Accurate signal collection and application are the foundation of these measurements, but a long-term issue is the signal distortion resulting from the interface gap. The height of the gap is the key characteristic needed to evaluate or model the distortion, but it is difficult to measure. By integrating a pair of nanopores at the electronic sensor plane and measuring the ion conductance between them, we developed a versatile and straightforward strategy to realize the direct cooperative evaluation of the gap height during exocytotic release from adrenal gland tissues. The signaling distortion of this gap has been theoretically evaluated and shows almost no influence on the amperometric recording of exocytosis in a classic "semi-artificial synapse" configuration. This strategy should benefit research concerning various bio/chemical/machine interfaces.
Asunto(s)
Nanoporos , ElectrónicaRESUMEN
We have developed the means to simultaneously measure the physical size and count catecholamine molecules in individual nanometer transmitter vesicles. This is done by combining resistive pulse (RP) measurements in a nanopore pipet and vesicle impact electrochemical cytometry (VIEC) at an electrode as the vesicle exits the nanopore. Analysis of freshly isolated bovine adrenal vesicles shows that the size and internal catecholamine concentration of vesicles varies with the occurrence of a dense core inside the vesicles. These results might benefit the understanding about the vesicles maturation, especially involving the "sorting by retention" process and concentration increase of intravesicular catecholamine. The methodology is applicable to understanding soft nanoparticle collisions on electrodes, vesicles in exocytosis and phagocytosis, intracellular vesicle transport, and analysis of electroactive drugs in exosomes.
Asunto(s)
Catecolaminas/análisis , Gránulos Cromafines/química , Técnicas Electroquímicas/métodos , Nanoporos , Animales , Bovinos , Técnicas Electroquímicas/instrumentación , Electrodos , Tamaño de la PartículaRESUMEN
Remarkable progresses have been made in electrochemical monitoring of living cells based on one-dimensional (1D) or two-dimensional (2D) sensors, but the cells cultured on 2D substrate under these circumstances are departed from their three-dimensional (3D) microenvironments in vivo. Significant advances have been made in developing 3D culture scaffolds to simulate the 3D microenvironment yet most of them are insulated, which greatly restricts their application in electrochemical sensing. Herein, we propose a versatile strategy to endow 3D insulated culture scaffolds with electrochemical performance while granting their biocompatibility through conductive polymer coating. More specifically, 3D polydimethylsiloxane scaffold is uniformly coated by poly(3,4-ethylenedioxythiophene) and further modified by platinum nanoparticles. The integrated 3D device demonstrates desirable biocompatibility for long-term 3D cell culture and excellent electrocatalytic ability for electrochemical sensing. This allows real-time monitoring of reactive oxygen species release from cancer cells induced by a novel potential anticancer drug and reveals its promising application in cancer treatment. This work provides a new idea to construct 3D multifunctional electrochemical sensors, which will be of great significance for physiological and pathological research.
Asunto(s)
Técnicas de Cultivo de Célula , Técnicas Electroquímicas , Polímeros/química , Conductividad Eléctrica , Electrodos , Células HeLa , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Células MCF-7RESUMEN
Mitochondria are believed to be the major source of intracellular reactive oxygen species (ROS). However, in situ, real-time and quantitative monitoring of ROS release from mitochondria that are present in their cytosolic environment remains a great challenge. In this work, a platinized SiC@C nanowire electrode is placed into a single cell for in situ detection of ROS signals from intracellular mitochondria, and antineoplastic agent (paclitaxel) induced ROS production is successfully recorded. Further investigations indicate that complex IV (cytochrome c oxidase, COX) is the principal site for ROS generation, and significantly more ROS are generated from mitochondria in cancer cells than that from normal cells. This work provides an effective approach to directly monitor intracellular mitochondria by nanowire electrodes, and consequently obtains important physiological evidence on antineoplastic agent-induced ROS generation, which will be of great benefit for better understanding of chemotherapy at subcellular levels.
Asunto(s)
Electroquímica/métodos , Mitocondrias/metabolismo , Paclitaxel/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Línea Celular Tumoral , Electrodos , Humanos , Ratones , Mitocondrias/efectos de los fármacos , Células 3T3 NIH , Nanocables/químicaRESUMEN
The existence of a homeostatic mechanism regulating reactive oxygen/nitrogen species (ROS/RNS) amounts inside phagolysosomes has been invoked to account for the efficiency of this process but could not be unambiguously documented. Now, intracellular electrochemical analysis with platinized nanowire electrodes (Pt-NWEs) allowed monitoring ROS/RNS effluxes with sub-millisecond resolution from individual phagolysosomes impacting onto the electrode inserted inside a living macrophage. This shows for the first time that the consumption of ROS/RNS by their oxidation at the nanoelectrode surface stimulates the production of significant ROS/RNS amounts inside phagolysosomes. These results establish the existence of the long-postulated ROS/RNS homeostasis and allows its kinetics and efficiency to be quantified. ROS/RNS concentrations may then be maintained at sufficiently high levels for sustaining proper pathogen digestion rates without endangering the macrophage internal structures.
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Técnicas Electroquímicas/métodos , Electrodos , Homeostasis , Macrófagos/metabolismo , Fagosomas/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Células Cultivadas , Macrófagos/citología , Ratones , Oxidación-ReducciónRESUMEN
Current achievements on electrochemical monitoring of cells are often gained on two-dimensional (2D) substrates, which fail in mimicking the cellular environments and accurately reproducing the cellular functions within a three-dimensional (3D) tissue. In this regard, 3D scaffold concurrently integrated with the function of cell culture and electrochemical sensing is conceivably a promising platform to monitor cells in real time under their in vivo-like 3D microenvironments. However, it is particularly challenging to construct such a multifunctional scaffold platform. Herein, we developed a 3-aminophenylboronic acid (APBA) functionalized graphene foam (GF) network, which combines the biomimetic property of APBA with the mechanical and electrochemical properties of GF. Hence, the GF network can serve as a 3D scaffold to culture cells for a long period with high viability and simultaneously as an electrode for highly sensitive electrochemical sensing. This allows monitoring of gaseous messengers H2S released from the cells cultured on the 3D scaffold in real time. This work represents considerable progress in fabricating 3D cell culture scaffold with electrochemical properties, thereby facilitating future studies of physiologically relevant processes.
Asunto(s)
Compuestos de Anilina/química , Materiales Biomiméticos/química , Ácidos Borónicos/química , Técnicas de Cultivo de Célula/métodos , Grafito/química , Andamios del Tejido/química , Biomimética , Técnicas Biosensibles/métodos , Adhesión Celular , Proliferación Celular , Técnicas Electroquímicas/métodos , Células HeLa , Humanos , Sulfuro de Hidrógeno/análisisRESUMEN
OBJECTIVE: To examine the association between habitual sleep duration and obesity among Chinese adults. METHODS: The association of sleep duration and obesity was investigated among 7,094 community-dwelling Chinese adults. Sleep duration was self-reported. In this study, obesity was defined as follows: body mass index (BMI) â 28 kg/m2, waist circumference (WC) â 85 cm in men and â 80 cm in women, and percent body fat (%BF) â 25 in men and â 35 in women. Logistic and quantile regressions were employed to examine relationships of interest. RESULTS: Overall, 6.42% of the participants reported short sleep durations (< 6 h/d) while 14.71% reported long (â 9 h/d) sleep durations. Long sleepers (â 9 h/d) represented a greater frequency of women with obesity [odds ratio (OR): 1.30; 95% confidence interval (CI), 1.02-1.67] and high body fat (1.43, 1.04-1.96) than those who slept 7-8 h/d. An association between long sleep times and higher BMI estimations was found across the 10th-75th percentile of the BMI distribution. Among men, long sleepers (â 9 h/d) presented lower risks of developing abdominal obesity compared with individuals who slept 7-8 h/d (OR = 0.79, 95% CI: 0.44-0.99). CONCLUSION: Our study suggests that long sleep durations are associated with general obesity in Chinese women but reduced waist circumferences in men. Confirmatory studies are needed to determine the heterogeneous association of sleep time and obesity by gender.
Asunto(s)
Tejido Adiposo/fisiología , Pueblo Asiatico , Índice de Masa Corporal , Sueño/fisiología , Circunferencia de la Cintura , Adulto , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Población Rural , Encuestas y Cuestionarios , Población UrbanaRESUMEN
Nanoelectrodes allow precise and quantitative measurements of important biological processes at the single living-cell level in real time. Cylindrical nanowire electrodes (NWEs) required for intracellular measurements create a great challenge for achieving excellent electrochemical and mechanical performances. Herein, we present a facile and robust solution to this problem based on a unique SiC-core-shell design to produce cylindrical NWEs with superior mechanical toughness provided by the SiC nano-core and an excellent electrochemical performance provided by the ultrathin carbon shell that can be used as such or platinized. The use of such NWEs for biological applications is illustrated by the first quantitative measurements of ROS/RNS in individual phagolysosomes of living macrophages. As the shell material can be varied to meet any specific detection purpose, this work opens up new opportunities to monitor quantitatively biological functions occurring inside cells and their organelles.
Asunto(s)
Nanocables/química , Especies de Nitrógeno Reactivo/análisis , Especies Reactivas de Oxígeno/análisis , Animales , Compuestos Inorgánicos de Carbono/química , Técnicas Electroquímicas , Electrodos , Células HeLa , Humanos , Macrófagos/citología , Macrófagos/metabolismo , Ratones , Microscopía Fluorescente , Fagosomas/metabolismo , Células RAW 264.7 , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Silicona/químicaRESUMEN
Biosensors always suffer from passivation that prevents their reutilization. To address this issue, photocatalytically renewable sensors composed of semiconductor photocatalysts and sensing materials have emerged recently. In this work, we developed a robust and versatile method to construct different kinds of renewable biosensors consisting of ZnO nanorods and nanostructured Au. Via a facile and efficient photochemical reduction, various nanostructured Au was obtained successfully on ZnO nanorods. As-prepared sensors concurrently possess excellent sensing capability and desirable photocatalytic cleaning performance. Experimental results demonstrate that dendritic Au/ZnO composite has the strongest surface-enhanced Raman scattering (SERS) enhancement, and dense Au nanoparticles (NPs)/ZnO composite has the highest electrochemical activity, which was successfully used for electrochemical detection of NO release from cells. Furthermore, both of the SERS and electrochemical sensors can be regenerated efficiently for renewable applications via photodegrading adsorbed probe molecules and biomolecules. Our strategy provides an efficient and versatile method to construct various kinds of highly sensitive renewable sensors and might expand the application of the photocatalytically renewable sensor in the biosensing area.
Asunto(s)
Técnicas Biosensibles/instrumentación , Oro/química , Nanopartículas del Metal/química , Nanotubos/química , Óxido de Zinc/química , Catálisis , Cloruros/química , Equipo Reutilizado , Compuestos de Oro/química , Oxidación-Reducción , Procesos Fotoquímicos , Espectrometría RamanRESUMEN
OBJECTIVE: To understand the associations of physical activity domains with metabolic syndrome among a middle-aged Chinese population. METHODS: In all, 3326 professional adults aged 35-64 years from Beijing and Zhejiang province were recruited with a cluster random sampling method. The Global Physical Activity Questionnaire was modified, and the recommended Asia-Pacific cut-offs of waist circumstance were introduced into the criteria for metabolic syndrome from the Adult Treatment Panel III. A binary logistic regression model was applied to examine the association of all physical activity domains with the risk of the syndrome. RESULTS: Participants who engaged in domestic activity for â1176 MET-min/week had a 41.6% less chance of having metabolic syndrome [odds ratio (OR), 0.584; 95% confidence interval (CI), 0.480-0.710] than those without this activity. In adjusted models, adults who actively commuted for â33 MET-min/week but <528 MET-min/week had a 25% less chance of having the syndrome (OR, 0.750; 95% CI, 0.582-0.966) than those who did not. No interaction was detected between the two domains of activity and the syndrome. CONCLUSION: This study highlighted the independently negative association of traffic and house activity with the prevalence of the syndrome in this sample with a generally low level of moderate activity.
Asunto(s)
Actividades Cotidianas , Ciclismo/fisiología , Síndrome Metabólico , Actividad Motora/fisiología , Caminata/fisiología , Adulto , Presión Sanguínea/fisiología , Índice de Masa Corporal , Tamaño Corporal , China , Ejercicio Físico/fisiología , Humanos , Lípidos/sangre , Modelos Logísticos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/etiología , Persona de Mediana Edad , Distribución Aleatoria , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
Chemical synaptic transmission is central to the brain functions. In this regard, real-time monitoring of chemical synaptic transmission during neuronal communication remains a great challenge. In this work, inâ vivo-like oriented neural networks between superior cervical ganglion (SCG) neurons and their effector smooth muscle cells (SMC) were assembled in a microfluidic device. This allowed amperometric detection of individual neurotransmitter release events inside functional SCG-SMC synapse with carbon fiber nanoelectrodes as well as recording of postsynaptic potential using glass nanopipette electrodes. The high vesicular release activities essentially involved complex events arising from flickering fusion pores as quantitatively established based on simulations. This work allowed for the first time monitoring inâ situ chemical synaptic transmission under conditions close to those found inâ vivo, which may yield important and new insights into the nature of neuronal communications.
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Potenciales Postsinápticos Excitadores/fisiología , Unión Neuromuscular/metabolismo , Sinapsis/metabolismo , Animales , Células Cultivadas , Técnicas de Cocultivo , Técnicas Electroquímicas , Electrodos , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Microscopía Fluorescente , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Nanoestructuras/química , Unión Neuromuscular/química , Neurotransmisores/metabolismo , Ganglio Cervical Superior/citología , Ganglio Cervical Superior/metabolismo , Transmisión SinápticaRESUMEN
Electrode fouling and passivation is a substantial and inevitable limitation in electrochemical biosensing, and it is a great challenge to efficiently remove the contaminant without changing the surface structure and electrochemical performance. Herein, we propose a versatile and efficient strategy based on photocatalytic cleaning to construct renewable electrochemical sensors for cell analysis. This kind of sensor was fabricated by controllable assembly of reduced graphene oxide (RGO) and TiO2 to form a sandwiching RGO@TiO2 structure, followed by deposition of Au nanoparticles (NPs) onto the RGO shell. The Au NPs-RGO composite shell provides high electrochemical performance. Meanwhile, the encapsulated TiO2 ensures an excellent photocatalytic cleaning property. Application of this renewable microsensor for detection of nitric oxide (NO) release from cells demonstrates the great potential of this strategy in electrode regeneration and biosensing.
Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas/instrumentación , Catálisis , Células Endoteliales de la Vena Umbilical Humana , Humanos , Microscopía Electrónica de Rastreo , Óxido Nítrico/análisisRESUMEN
Angiosarcomas account for a mere 2-3% of adult soft tissue sarcomas, with an overall poor outcome. Depending on the primary site, angiosarcomas have distinct prognosis. Primary hepatic angiosarcomas (PHAs) are much rare tumors, with worse prognosis compared with other angiosarcomas. PHA is reported to be associated with vinyl chloride, but the majority of patients were still with unknown etiology. As PHA lacks specific symptoms, signs, or images, pathological diagnosis is necessary. The review summarizes 25 articles published from January 2000 to December 2012, including 64 cases of PHA with detailed information. Survival curves are estimated using the Kaplan-Meier method by SPSS 21.0. We find that the median survival time is 5 months; local excision alone or combination with adjuvant therapy is the optimal choice, with median survival time of 17 months. In addition, liver transplant is abandoned for high recurrence rate; emergent transcatheter arterial embolization is thought to be an efficient method for controlling intra-abdominal bleeding; and transcatheter arterial chemoembolization and chemotherapy may be helpful in improving survival.
Asunto(s)
Hemangiosarcoma/terapia , Neoplasias Hepáticas/terapia , Adulto , Anciano , Preescolar , Terapia Combinada , Embolización Terapéutica/métodos , Femenino , Hemangiosarcoma/diagnóstico , Hemangiosarcoma/etiología , Hemangiosarcoma/mortalidad , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Pronóstico , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Cloruro de Vinilo/efectos adversosRESUMEN
Chemical neurotransmission occurs at chemical synapses and endocrine glands, but up to now there was no means for direct monitoring of neurotransmitter exocytosis fluxes and their precise kinetics from inside an individual synapse. The fabrication of a novel finite conical nanoelectrode is reported perfectly suited in size and electrochemical properties for probing amperometrically inside what appears to be single synapses and monitoring individual vesicular exocytotic events in real time. This allowed obtaining direct and important physiological evidences which may yield important and new insights into the nature of synaptic communications.
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Técnicas Electroquímicas/instrumentación , Exocitosis , Neuronas/citología , Sinapsis/metabolismo , Animales , Células Cultivadas , Diseño de Equipo , Microelectrodos , Nanotecnología , Neuronas/metabolismo , Neurotransmisores/metabolismo , Ganglio Cervical Superior/citologíaRESUMEN
Airborne nanoplastics can enter alveolar cells and trigger intracellular oxidative stress primarily. Herein, taking advantage of the high electrochemical resolution of SiC@Pt nanoelectrodes, we achieved the quantitative discrimination of the major ROS/RNS within A549 cells, disclosed the sources of their precursors, and observed that the NO (RNS precursor) level significantly increased, whereas O2Ë- (ROS precursor) remained relatively stable during the nanoplastics exposure. This establishes that iNOS or mitochondrion-targeted treatment may be a preventive or therapeutic strategy for nanoplastic-induced lung injury.
Asunto(s)
Técnicas Electroquímicas , Especies de Nitrógeno Reactivo , Especies Reactivas de Oxígeno , Humanos , Especies Reactivas de Oxígeno/metabolismo , Células A549 , Especies de Nitrógeno Reactivo/metabolismo , Estrés Oxidativo/efectos de los fármacos , ElectrodosRESUMEN
Exposure to widely used inert fibrous nanomaterials (for example, glass fibres or carbon nanotubes) may result in asbestos-like lung pathologies, becoming an important environmental and health concern. However, the origin of the pathogenesis of such fibres has not yet been clearly established. Here we report an electrochemical nanosensor that is used to monitor and quantitatively characterize the flux and dynamics of reactive species release during the frustrated phagocytosis of glass nanofibres by single macrophages. We show the existence of an intense prolonged release of reactive oxygen and nitrogen species by single macrophages near their phagocytic cups. This continued massive leakage of reactive oxygen and nitrogen species damages peripheral cells and eventually translates into chronic inflammation and lung injury, as seen during in vitro co-culture and in vivo experiments.