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

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Particle and Fibre Toxicology

, 2:3

First Online: 27 June 2005Received: 01 December 2004Accepted: 27 June 2005


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, Ir-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 Ir isotope. Lung permeability by the use of Tc-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 Tc-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.

Keywordsendothelium translocation ultrafine particles isolated perfused lung permeability. Electronic supplementary materialThe online version of this article doi:10.1186-1743-8977-2-3 contains supplementary material, which is available to authorized users.

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Autor: James J Meiring - Paul JA Borm - Karim Bagate - Manuela Semmler - Jürgen Seitz - Shinji Takenaka - Wolfgang G Kreyling


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