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      Assessing particle and fiber toxicology in the respiratory system: the stereology toolbox

      review-article
      , ,
      Particle and Fibre Toxicology
      BioMed Central

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          Abstract

          The inhalation of airborne particles can lead to pathological changes in the respiratory tract. For this reason, toxicology studies on effects of inhalable particles and fibers often include an assessment of histopathological alterations in the upper respiratory tract, the trachea and/or the lungs. Conventional pathological evaluations are usually performed by scoring histological lesions in order to obtain “quantitative” information and an estimation of the severity of the lesion. This approach not only comprises a potential subjective bias, depending on the examiner’s judgment, but also conveys the risk that mild alterations escape the investigator’s eye. The most accurate way of obtaining unbiased quantitative information about three-dimensional (3D) features of tissues, cells, or organelles from two-dimensional physical or optical sections is by means of stereology, the gold standard of image-based morphometry. Nevertheless, it can be challenging to express histopathological changes by morphometric parameters such as volume, surface, length or number only. In this review we therefore provide an overview on different histopathological lesions in the respiratory tract associated with particle and fiber toxicology and on how to apply stereological methods in order to correctly quantify and interpret histological lesions in the respiratory tract. The article further aims at pointing out common pitfalls in quantitative histopathology and at providing some suggestions on how respiratory toxicology can be improved by stereology. Thus, we hope that this article will stimulate scientists in particle and fiber toxicology research to implement stereological techniques in their studies, thereby promoting an unbiased 3D assessment of pathological lesions associated with particle exposure.

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          Most cited references93

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          The unbiased estimation of number and sizes of arbitrary particles using the disector.

          D Sterio (1984)
          A three-dimensional counting rule and its integral test system, the disector, for obtaining unbiased estimates of the number of arbitrary particles in a specimen is presented. Used in combination with ordinary and recently developed stereological methods unbiased estimates of various mean particle sizes and the variance of particle volume are obtainable on sets of two parallel sections with a known separation. The same principle allows the unbiased estimation of the distribution of individual particle volumes in sets of serial sections.
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            Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers.

            Several epidemiologic studies have demonstrated a consistent association between levels of particulate matter (PM) in the ambient air with increases in cardiovascular and respiratory mortality and morbidity. Diesel exhaust (DE), in addition to generating other pollutants, is a major contributor to PM pollution in most places in the world. Although the epidemiologic evidence is strong, there are as yet no established biological mechanisms to explain the toxicity of PM in humans. To determine the impact of DE on human airways, we exposed 15 healthy human volunteers to air and diluted DE under controlled conditions for 1 h with intermittent exercise. Lung functions were measured before and after each exposure. Blood sampling and bronchoscopy were performed 6 h after each exposure to obtain airway lavages and endobronchial biopsies. While standard lung function measures did not change following DE exposure, there was a significant increase in neutrophils and B lymphocytes in airway lavage, along with increases in histamine and fibronectin. The bronchial biopsies obtained 6 h after DE exposure showed a significant increase in neutrophils, mast cells, CD4+ and CD8+ T lymphocytes along with upregulation of the endothelial adhesion molecules ICAM-1 and VCAM-1, with increases in the numbers of LFA-1+ cells in the bronchial tissue. Significant increases in neutrophils and platelets were observed in peripheral blood following DE exposure. This study demonstrates that at high ambient concentrations, acute short-term DE exposure produces a well-defined and marked systemic and pulmonary inflammatory response in healthy human volunteers, which is underestimated by standard lung function measurements.
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              Notes on the estimation of the numerical density of arbitrary profiles: the edge effect

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                Author and article information

                Contributors
                brandenberger.christina@mh-hannover.de
                ochs.matthias@mh-hannover.de
                muehlfeld.christian@mh-hannover.de
                Journal
                Part Fibre Toxicol
                Part Fibre Toxicol
                Particle and Fibre Toxicology
                BioMed Central (London )
                1743-8977
                31 October 2015
                31 October 2015
                2015
                : 12
                : 35
                Affiliations
                [ ]Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
                [ ]Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover, Germany
                [ ]Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany
                Article
                110
                10.1186/s12989-015-0110-8
                4628359
                26521139
                8a8c811b-c98a-4e4d-8aab-b23767207ac4
                © Brandenberger et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 7 June 2015
                : 14 October 2015
                Categories
                Review
                Custom metadata
                © The Author(s) 2015

                Toxicology
                Toxicology

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