Biomedical subjects

Wolfgang G Kreyling

Publications and source records attributed to Wolfgang G Kreyling.

10 recordsLinked to original sources

PubMed2006

Motion and twisting of magnetic particles ingested by alveolar macrophages in the human lung: effect of smoking and disease.

BACKGROUND: Magnetic microparticles being ingested by alveolar macrophages can be used as a monitor for intracellular phagosome motions and cytoskeletal mechanical properties. These studies can be performed in the human lung after voluntary inhalation. The influence of cigarette smoking and lung diseases on cytoskeleton dependent functions was studied. METHODS: Spherical 1.3 microm diameter ferrimagnetic iron oxide particles were inhaled by 17 healthy volunteers (40-65 years), 15 patients with sarcoidosis (SAR), 12 patients with idiopathic pulmonary fibrosis (IPF), and 18 patients with chronic obstructive bronchitis (COB). The retained particles were magnetized and aligned in an external 100 mT magnetic field. All magnetized particles induce a weak magnetic field of the lung, which was detected by a sensitive SQUID (superconducting quantum interference device) sensor. Cytoskeletal reorganizations within macrophages and intracellular transport cause stochastic magnetic dipole rotations, which are reflected in a decay of the magnetic lung field, called relaxation. Directed phagosome motion was induced in a weak magnetic twisting field. The resistance of the cytoplasm to particle twisting was characterized by the viscosity and the stiffness (ratio between stress to strain) of the cytoskeleton. RESULTS: One week after particle inhalation and later macrophage motility (relaxation) and cytoskeletal stiffness was not influenced by cigarette smoking, neither in healthy subjects, nor in the patients. Patients with IPF showed in tendency a faster relaxation (p = 0.06). Particle twisting revealed a non-Newtonian viscosity with a pure viscous and a viscoelastic compartment. The viscous shear was dominant, and only 27% of the shear recoiled and reflected viscoelastic properties. In patients with IPF, the stiffness was reduced by 60% (p < 0.02). An analysis of the shear rate and stress dependence of particle twisting allows correlating the rheological compartments to cytoskeletal subunits, in which microtubules mediate the pure viscous (non-recoverable) shear and microfilaments mediate the viscoelastic (recoverable) behavior. The missing correlation between relaxation and particle twisting shows that both stochastic and directed phagosome motion reflect different cytoskeletal mechanisms. CONCLUSION: Faster relaxation and a soft cytoskeleton in patients with IPF indicate alterations in cytoskeleton dependent functions of alveolar macrophages, which may cause dysfunction's in the alveolar defense, like a slower migration, a retarded phagocytosis, a disturbed phagosome lysosome fusion and an impaired clearance.

Journal Article↗

PubMed2006

No significant translocation of inhaled 35-nm carbon particles to the circulation in humans.

Human pulmonary retention of 35 nm 99mTc-labeled carbonaceous particles, produced with a modified Technegas generator, was followed for 24 h using a gamma camera imaging technique. Nine healthy subjects and four asthmatics inhaled the test particles. Particle labeling stability was tested in vitro during 48 h. We also measured in vivo leaching in blood and in urine for 24 h. One additional subject was exposed to particles with unstable labeling. There were no significant differences between healthy and asthmatic subjects in any of the parameters studied. Particle retention after 24 h was 102% (SD +/- 4.7). Cumulative in vitro leaching of 99mTc activity from the particles was 1.7% (+/-1.1) after 24 h. In blood samples, 80 min after exposure, 1.1% (+/- 0.4) of initially deposited activity was detected and 91% of the activity was not bound to particles. In urine sampled during the first 24 h after exposure, 3.6% (+/- 0.9) of lung deposited activity was detected. Lung retention was 30% after 1 h in the subject exposed to the leaching aerosol (n = 1). Thirty-one percent of the deposited activity was detected in the blood after 80 min and 80% was not bound to particles. Fifty percent of the activity was excreted with urine within 24 h. On gamma camera images the activity visibly translocated from lungs to thyroid and gastrointestinal tract. In conclusion, over a 24-h period there was no significant translocation of inhaled 35-nm particles to the systemic circulation.

Aerosols↗

PubMed2006

Ultrafine particle-lung interactions: does size matter?

Epidemiological studies continue to indicate associations between exposure to increased concentrations of ambient fine and ultrafine particles and adverse health effects in susceptible individuals. The ultrafine particle fraction in the ambient atmosphere seems to play a specific role. Yet, the dosimetry (including deposition patterns in the respiratory tract and, particularly, the biokinetic fate of ultrafine particles) is not fully understood. In contrast to fine particles, inhaled ultrafine particles seem to follow different routes in the organism. Cardiovascular effects observed in epidemiological studies triggered the discussion on enhanced translocation of ultrafine particles from the respiratory epithelium towards circulation and subsequent target organs, such as heart, liver, and brain, eventually causing adverse effects on cardiac function and blood coagulation, as well as on functions of the central nervous system. Current knowledge on systemic translocation of ultrafine particles in humans and animal models is reviewed. Additionally, an estimate of accumulating particle numbers in secondary target organs during chronic exposure is extrapolated from long-term translocation data obtained from rats. Toxicological studies aim to provide the biological plausibility of health effects of ultrafine particles and to identify cascades of mechanisms that are causal for the gradual transition from the physiological status towards pathophysiologcal alterations and eventually chronic disease. Considering the interaction between insoluble ultrafine particles and biological systems (such as body fluids, proteins, and cells), there still are gaps in the current knowledge on how ultrafine particles may cause adverse reactions. This paper reviews the current concept of interactions between insoluble ultrafine particles and biological systems.

Aerosols↗

PubMed2005

Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium.

BACKGROUND: Particulate air pollution is reported to cause adverse health effects in susceptible individuals. Since most of these particles are derived form combustion processes, the primary composition product is carbon with a very small diameter (ultrafine, less than 100 nm in diameter). Besides the induction of reactive oxygen species and inflammation, ultrafine particles (UFP) can cause intracellular calcium transients and suppression of defense mechanisms of alveolar macrophages, such as impaired migration or phagocytosis. METHODS: In this study the role of intracellular calcium transients caused by UFP was studied on cytoskeleton related functions in J774A.1 macrophages. Different types of fine and ultrafine carbon black particles (CB and ufCB, respectively), such as elemental carbon (EC90), commercial carbon (Printex 90), diesel particulate matter (DEP) and urban dust (UD), were investigated. Phagosome transport mechanisms and mechanical cytoskeletal integrity were studied by cytomagnetometry and cell viability was studied by fluorescence microscopy. Macrophages were exposed in vitro with 100 and 320 microg UFP/ml/million cells for 4 hours in serum free medium. Calcium antagonists Verapamil, BAPTA-AM and W-7 were used to block calcium channels in the membrane, to chelate intracellular calcium or to inhibit the calmodulin signaling pathways, respectively. RESULTS: Impaired phagosome transport and increased cytoskeletal stiffness occurred at EC90 and P90 concentrations of 100 microg/ml/million cells and above, but not with DEP or UD. Verapamil and W-7, but not BAPTA-AM inhibited the cytoskeletal dysfunctions caused by EC90 or P90. Additionally the presence of 5% serum or 1% bovine serum albumin (BSA) suppressed the cytoskeletal dysfunctions. Cell viability showed similar results, where co-culture of ufCB together with Verapamil, W-7, FCS or BSA produced less cell dead compared to the particles only.

Journal Article↗

PubMed2005

The influence of hydrogen peroxide and histamine on lung permeability and translocation of iridium nanoparticles in the isolated perfused rat lung.

BACKGROUND: Translocation of ultrafine particles (UFP) into the blood that returns from the lungs to the heart has been forwarded as a mechanism for particle-induced cardiovascular effects. The objective of this study was to evaluate the role of the endothelial barrier in the translocation of inhaled UFP from the lung into circulation. METHODS: The isolated perfused rat lung (IPRL) was used under negative pressure ventilation, and radioactive iridium particles (18 nm, CMD, 192Ir-UFP) were inhaled during 60 minutes to achieve a lung burden of 100-200 microg. Particle inhalation was done under following treatments: i) control perfusion, ii) histamine (1 microM) in perfusate, iii) luminal histamine instillation (1 mM), and iv) luminal instillation of H2O2. Particle translocation to the perfusate was assessed by the radioactivity of 192Ir isotope. Lung permeability by the use of Tc99m-labeled diethylene triamine pentaacetic acid (DTPA). In addition to light microscopic morphological evaluation of fixed lungs, alkaline phosphatase (AKP) and angiotensin converting enzyme (ACE) in perfusate were measured to assess epithelial and endothelial integrity. RESULTS: Particle distribution in the lung was homogenous and similar to in vivo conditions. No translocation of Ir particles at negative pressure inhalation was detected in control IPL, but lungs pretreated with histamine (1 microM) in the perfusate or with luminal H2O2 (0.5 mM) showed small amounts of radioactivity (2-3 % dose) in the single pass perfusate starting at 60 min of perfusion. Although the kinetics of particle translocation were different from permeability for 99mTc-DTPA, the pretreatments (H2O2, vascular histamine) caused similar changes in the translocation of particles and soluble mediator. Increased translocation through epithelium and endothelium with a lag time of one hour occurred in the absence of epithelial and endothelial damage. CONCLUSION: Permeability of the lung barrier to UFP or nanoparticles is controlled both at the epithelial and endothelial level. Conditions that affect this barrier function such as inflammation may affect translocation of NP.

Journal Article↗

PubMed2005

Relationship between different size classes of particulate matter and meteorology in three European cities.

Evidence on the correlation between particle mass and (ultrafine) particle number concentrations is limited. Winter- and spring-time measurements of urban background air pollution were performed in Amsterdam (The Netherlands), Erfurt (Germany) and Helsinki (Finland), within the framework of the EU funded ULTRA study. Daily average concentrations of ambient particulate matter with a 50% cut off of 2.5 microm (PM2.5), total particle number concentrations and particle number concentrations in different size classes were collected at fixed monitoring sites. The aim of this paper is to assess differences in particle concentrations in several size classes across cities, the correlation between different particle fractions and to assess the differential impact of meteorological factors on their concentrations. The medians of ultrafine particle number concentrations were similar across the three cities (range 15.1 x 10(3)-18.3 x 10(3) counts cm(-3)). Within the ultrafine particle fraction, the sub fraction (10-30 nm) made a higher contribution to particle number concentrations in Erfurt than in Helsinki and Amsterdam. Larger differences across the cities were found for PM2.5(range 11-17 microg m(-3)). PM2.5 and ultrafine particle concentrations were weakly (Amsterdam, Helsinki) to moderately (Erfurt) correlated. The inconsistent correlation for PM2.5 and ultrafine particle concentrations between the three cities was partly explained by the larger impact of more local sources from the city on ultrafine particle concentrations than on PM2.5, suggesting that the upwind or downwind location of the measuring site in regard to potential particle sources has to be considered. Also, relationship with wind direction and meteorological data differed, suggesting that particle number and particle mass are two separate indicators of airborne particulate matter. Both decreased with increasing wind speed, but ultrafine particle number counts consistently decreased with increasing relative humidity, whereas PM2.5 increased with increasing barometric pressure. Within the ultrafine particle mode, nucleation mode (10-30 nm) and Aitken mode (30-100 nm) had distinctly different relationships with accumulation mode particles and weather conditions. Since the composition of these particle fractions also differs, it is of interest to test in future epidemiological studies whether they have different health effects.

Air Pollutants↗

PubMed2004

Health effects of particles in ambient air.

A summary of a critical review by a working group of the German commission on Air Pollution Prevention of VDI and DIN of the actual data on exposure and health effects (excluding cancer) of fine particulate air pollution is presented. EXPOSURE: Typical ambient particle concentrations for PM10 (PM2.5) in Germany are in the range of 10-45 (10-30) microg/m3 as annual mean and 50-200 (40-150) microg/m3 as maximum daily mean. The ratio of PM2.5/PM10 generally amounts between 0.7 and 0.9. HEALTH EFFECTS: During the past 10 years many new epidemiological and toxicological studies on health effects of particulate matter (PM) have been published. In summary, long-term exposure against PM for years or decades is associated with elevated total, cardiovascular, and infant mortality. With respect to morbidity, respiratory symptoms, lung growth, and function of the immune system are affected. Short-term studies show consistant associations of exposure to daily concentrations of PM with mortality and morbidity on the same day or the subsequent days. Patients with asthma, COPD, pneumonia, and other respiratory diseases as well as patients with cardio-vascular diseases and diabetes are especially affected. The strongest associations are found for PM2.5 followed by PM10, with no indication of a threshold value for the health effects. The data base for ultra fine particles is too small for final conclusions. The available toxicological data support the epidemiological findings and give hints as to the mechanisms of the effects. CONCLUSION: The working group concludes that a further reduction of the limit values proposed for 2005 will substantially reduce health risks due to particulate air pollution. Because of the strong correlation of PM10 with PM2.5 at most German sites there is no specific need for limit values of PM2.5 for Germany in addition to those of PM10.

Air Pollutants↗

PubMed2004

Dosimetry and toxicology of ultrafine particles.

While epidemiological studies indicate an association between adverse health effects and ambient ultrafine particle concentrations in susceptible individuals, toxicological studies aim to identify mechanisms which are causal for the gradual transition from the physiological status towards patho-physiological disease. Impressive progress has been made in recent years when objectives changed from classical tests like lung function, etc. to endpoints comprising of particle induced oxidative stress, cell signaling and activation, release of mediators initiating inflammatory processes not only in the respiratory tract but also in the cardio-vascular system. Particularly, the large surface area of ultrafine particles provides a unique interface for catalytic reactions of surface-located agents with biological targets like proteins, cells, etc. However, toxicological studies are hampered by a number of imminent complications when simulating long-term exposure of humans in urban environments with inherited and/or acquired susceptibility (e.g., acute exposure studies at high concentrations either in human subjects or animal models). Yet, based on a conservative estimate results available begin to show an adverse health risk for susceptible individuals and support the epidemiological evidence.

Aerosols↗

PubMed2004

Effects of particulate air pollution on blood pressure and heart rate in subjects with cardiovascular disease: a multicenter approach.

Given the hypothesis that air pollution is associated with elevated blood pressure and heart rate, the effect of daily concentrations of air pollution on blood pressure and heart rate was assessed in 131 adults with coronary heart disease in Helsinki, Finland; Erfurt, Germany; and Amsterdam, the Netherlands. Blood pressure was measured by a digital monitor, and heart rate was calculated as beats per minute from an electrocardiogram recording with the patient in supine position. Particle concentrations were measured at central measuring sites. Linear regression was used to model the association between 24-hr mean concentrations of particles and blood pressure and heart rate. Estimates were adjusted for trend, day of week, temperature, barometric pressure, relative humidity, and medication use. Pooled effect estimates showed a small significant decrease in diastolic and systolic blood pressure in association with particulate air pollution; a slight decrease in heart rate was found. Of the three centers, Erfurt revealed the most consistent particle effects. The results do not support findings from previous studies that had shown an increase in blood pressure and heart rate in healthy individuals in association with particles. However, particle effects might differ in cardiac patients because of medication intake and disease status, both affecting the autonomic control of the heart.

Adult↗

PubMed2002

Particulate air pollution and risk of ST-segment depression during repeated submaximal exercise tests among subjects with coronary heart disease: the Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air (ULTRA) study.

BACKGROUND: Daily variations in ambient particulate air pollution have been associated with cardiovascular mortality and morbidity. We therefore assessed the associations between levels of the 3 main modes of urban aerosol distribution and the occurrence of ST-segment depressions during repeated exercise tests. METHODS AND RESULTS: Repeated biweekly submaximal exercise tests were performed during 6 months among adult subjects with stable coronary heart disease in Helsinki, Finland. Seventy-two exercise-induced ST-segment depressions >0.1 mV occurred during 342 exercise tests among 45 subjects. Simultaneously, particle mass <2.5 microm (PM2.5) and the number concentrations of ultrafine particles (particle diameter 10 to 100 nm [NC(0.01-0.1)]) and accumulation mode particles (100 to 1000 nm [NC(0.1-1)]) were monitored at a central site. Levels of particulate air pollution 2 days before the clinic visit were significantly associated with increased risk of ST-segment depression during exercise test. The association was most consistent for measures of particles reflecting accumulation mode particles (odds ratio 3.29; 95% CI, 1.57 to 6.92 for NC(0.1-1) and 2.84; 95% CI, 1.42 to 5.66 for PM2.5), but ultrafine particles also had an effect (odds ratio 3.14; 95% CI, 1.56 to 6.32), which was independent of PM2.5. Also, gaseous pollutants NO2 and CO were associated with an increased risk for ST-segment depressions. No consistent association was observed for coarse particles. The associations tended to be stronger among subjects who did not use beta-blockers. CONCLUSIONS: The present results suggest that the effect of particulate air pollution on cardiovascular morbidity is at least partly mediated through increased susceptibility to myocardial ischemia.

Adult↗