Tissue Optical Clearing, Three-Dimensional Imaging, and Computer Morphometry in Whole Mouse Lungs and Human Airways

Scott, Gregory D.; Blum, Emily; Fryer, A.D.; Jacoby, David B.

doi:10.1165/rcmb.2013-0284oc

Cited by 58 publications

(64 citation statements)

References 44 publications

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“…Here, we measured airway and nerve‐associated eosinophils in small noncartilaginous airways and in large cartilaginous airways separately, since nerve density decreases from proximal to distal airways (Scott et al. ). Small airways were characterized by more eosinophils overall, and more nerve‐associated eosinophils compared to large airways.…”

Section: Discussionmentioning

confidence: 99%

Ozone-induced eosinophil recruitment to airways is altered by antigen sensitization and tumor necrosis factor-αblockade

et al. 2017

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Ozone is an atmospheric pollutant that causes lung inflammation and airway hyperresponsiveness. Ozone's effects occur in two distinct phases that are mediated by different populations of eosinophils. In the acute phase 1 day after exposure, mature airway‐resident eosinophils alter parasympathetic nerve function that results in airway hyperresponsiveness. At this time point, the severity of hyperresponsiveness correlates with the number of eosinophils in close proximity to airway nerves, but not with eosinophils in bronchoalveolar lavage. Three days later, newly divided eosinophils are recruited to airways by a tumor necrosis factor‐α‐dependent mechanism. These new eosinophils paradoxically attenuate ozone‐induced airway hyperresponsiveness. Ozone's effects on airway tissue eosinophils and nerve‐associated eosinophils 3 days after exposure are unknown. Thus, we tested ozone's effects on eosinophils in airway subepithelium and around airway nerves 1 and 3 days after ozone in nonsensitized and ovalbumin‐sensitized guinea pigs with or without the tumor necrosis factor‐α antagonist, etanercept, and compared changes in eosinophils with ozone‐induced airway hyperresponsiveness. More eosinophils were present in small, noncartilaginous airways and along small airway nerves compared to large cartilaginous airways in all treatment groups. The number of airway and nerve‐associated eosinophils were unaffected 1 day after ozone exposure, whereas significantly fewer airway eosinophils were present 3 days later. Airway and nerve‐associated eosinophils were also decreased in small airways 3 days after ozone in sensitized animals. These changes were blocked by etanercept. Airway eosinophils, but not nerve‐associated or bronchoalveolar lavage eosinophils correlated with airway hyperresponsiveness 3 days after ozone. Our findings indicate ozone causes persistent alterations in airway eosinophils and reinforce the importance of characterizing eosinophils’ effects within distinct airway compartments.

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Section: Discussionmentioning

confidence: 99%

Ozone-induced eosinophil recruitment to airways is altered by antigen sensitization and tumor necrosis factor-αblockade

et al. 2017

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“…Although unbiased stereological methods are available (104) and have been applied to airways (39), additional morphometric approaches are desirable. Two remarkable papers by Scott et al (134,135) have provided new ways of quantifying nerve fibres in the respiratory tract. Although the light microscopic approach does not differentiate between nerve fibres containing one or more axons, it provides comprehensive information on length, diameter, branching points, and the number of ganglia.…”

Section: Articles Addressing Methodological Improvementsmentioning

confidence: 99%

“…In the first paper of this group (134), airways were prepared by microdissection and computer-based morphometry was used to quantify structures. In the second paper (135), the authors applied tissue clearing to whole mouse lungs and thus enabled the visualization of airway innervation in 3D and correlating with, for instance, the airway generation.…”

Section: Articles Addressing Methodological Improvementsmentioning

confidence: 99%

A review of recent developments and applications of morphometry/stereology in lung research

Mühlfeld

Hegermann

Wrede

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Here, we analyze the current use of morphometric and stereological methods in lung research and provide an overview on recent methodological developments and biological observations made by the use of stereology. Based on this analysis we hope to provide useful recommendations for a good stereological practice to further the use of advanced and unbiased stereological methods.design-based stereology; fibrosis; serial block face scanning electron microscopy; morphometry; emphysema DESIGN-BASED STEREOLOGY HAS been widely accepted as the gold standard of quantitative morphology in lung research. Approximately 50 yr after the beginning of Weibel's research on the structure-function relationships of the lung (160, 162), the American Thoracic Society and the European Respiratory Society published a joint research policy statement on the use of stereology for the quantitative assessment of lung structure (51), thereby providing a coherent framework for quantitative morphology in lung research. Still, the implementation of this theoretical framework into a practical research question remained challenging. This led us to provide a more practically and problem-oriented approach to lung stereology recently by addressing the pathology of various lung diseases and by making practical recommendations of useful stereological parameters for these diseases (101, 111).The current review article intends to provide an update on lung stereology over the last 2 yr, first by analyzing the use of stereological methods in the two basic lung research journals with the highest impact factor in recent years. Here, we discuss what stereological methods are currently most widely used and where there is still space for further improving the quality of quantitative morphology in lung research. In the second part of this article, we address recent methodological developments and advances, and we highlight new biological observations made by the use of stereology. Analysis of the Current Use of Stereology in Lung Research Selection of journals and articles. Among the journals dedicated to pulmonary research, we chose the American Journal of Physiology Lung Cellular and Molecular Physiology and the American Journal of Respiratory Cell and Molecular Biologyfor a literature review. The two journals were selected because they have the highest impact factor of those journals publishing basic lung science and because their impact factor has proven to be in the same range over the last years (87). Another important reason is the fact that both journals or their corresponding societies have made substantial efforts to increase the quality of morphometry in lung research by publishing research guidelines (51) and review articles (10, 101, 111) as well as editorials (47,89,162) dedicated to this topic. To identify target articles, all articles (except reviews) published in the print issues in 2013 and 2014 were searched for the terms "morphometry/morphometric" and "stereology/stereological." The selection of articles was then closely looked at to analyze w...

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“…As the biopsy material used in this study was obtained solely from patients with chronic cough, it is clear that a careful comparison between health and disease is required if we are to assign any disease-specific significance to the observations. There may, Am J Respir Crit Care Med Vol 192, Iss 1, pp 1-10, Jul 1, 2015 Internet address: www.atsjournals.org for example, be clinically relevant quantitative differences in nerves, and the recent advances in imaging technology in this field are likely to provide answers to such questions in the near future (15). However, what might be even more important than any quantitative difference in the nerves is alteration in their function.…”

Section: Sensing Real Progress In the Study Of Human Airway Nervesmentioning

confidence: 99%

Seeing Is Believing. Sensing Real Progress in the Study of Human Airway Nerves

McGarvey

2015

Am J Respir Crit Care Med

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Tissue Optical Clearing, Three-Dimensional Imaging, and Computer Morphometry in Whole Mouse Lungs and Human Airways

Cited by 58 publications

References 44 publications

Ozone-induced eosinophil recruitment to airways is altered by antigen sensitization and tumor necrosis factor-αblockade

Ozone-induced eosinophil recruitment to airways is altered by antigen sensitization and tumor necrosis factor-αblockade

A review of recent developments and applications of morphometry/stereology in lung research

Seeing Is Believing. Sensing Real Progress in the Study of Human Airway Nerves

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