Abstract
BackgroundTranslocation 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.MethodsThe 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 μg. Particle inhalation was done under following treatments: i) control perfusion, ii) histamine (1 μM 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.ResultsParticle 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 μM) 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.ConclusionPermeability 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.
Highlights
Epidemiological studies have demonstrated an increased morbidity and mortality by particulate air pollution [1,2]
Particle distribution and deposition The first set of experiments measured the distribution of 192Ir -ultrafine particles (UFP) related radioactivity in the lungs
(page number not for citation purposes) http://www.particleandfibretoxicology.com/content/2/1/3 kinetics of DTPA and particle translocation were different the in-situ treatments histamine and H2O2 caused unidirectional in both processes, in the absence of biochemical evidence for epithelial and endothelial damage
Summary
Epidemiological studies have demonstrated an increased morbidity and mortality by particulate air pollution [1,2]. The exact mechanism by which PM can adversely affect humans remains unknown, but several hypotheses have been forwarded These include that PM causes pulmonary inflammation causing release of factors that influence blood coagulation [3], reduced lung function [4], increased blood plasma viscosity [5], reduced heart rate variability [6,7] and destabilisation of atheromatous plagues [8]. Some of these effects are attributed to translocated nanoparticles based on their potential effects on vascular function [9,10], blood coagulation [11], mitochondrial function [12] and Ca-flow [13,14]. 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
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