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Using electron microscopes to look into the lung

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Abstract

In the nineteenth century, there was a dispute about the existence of a lung alveolar epithelium which remained unsolved until the invention of electron microscopy (EM) and its application to the lung. From the early 1960s, Ewald Weibel became the master of lung EM. He showed that the alveolar epithelium is covered with a lining layer containing surfactant. Weibel also explained the phenomenon of “non-nucleated plates” observed already in 1881 by Albert Kölliker. Weibel’s most significant contribution was to the development of stereological methods. Therefore, quantitative characterization of lung structure revealing structure–function relationships became possible. Today, the spectrum of EM methods to study the fine structure of the lung has been extended significantly. Cryo-preparation techniques are available which are necessary for immunogold labeling of molecules. Energy-filtering techniques can be used for the detection of elements. There have also been major improvements in stereology, thus providing a very versatile toolbox for quantitative lung phenotype analyses. A new dimension was added by 3D EM techniques. Depending on the desired sample size and resolution, the spectrum ranges from array tomography via serial block face scanning EM and focused ion beam scanning EM to electron tomography. These 3D datasets provide new insights into lung ultrastructure. Biomedical EM is an ever-developing field. Its high resolution remains unparalleled. Moreover, EM has the unique advantage of providing an “open view” into cells and tissues within their full architectural context. Therefore, EM will remain an indispensable tool for a better understanding of the lung’s functional design.

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Acknowledgments

Work from the authors’ laboratory was and is funded by the German Research Federation (DFG: OC23/7-3, 8-1, 9-3, 10-1; MU3118/2-1, KN916/1-1, SFB 587/TP B18; INST 192/504-1, INST 193/57-1; REBIRTH Cluster of Excellence), the Federal Ministry for Education and Research (BMBF: German Center for Lung Research DZL; 01DG14009) and the Swiss National Science Foundation (SNF: 116417, 121390, CRSII3_160704/1). The authors thank Dr. Hubert Schulz at the Training, Application and Support Center (TASC) of Carl Zeiss Microscopy, Oberkochen, Germany, for expert technical help with the FIB image acquisition and the generation of raw data sets at the Zeiss Application Center.

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Authors and Affiliations

  1. Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Matthias Ochs, Lars Knudsen, Jan Hegermann, Christoph Wrede, Roman Grothausmann & Christian Mühlfeld

  2. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany

    Matthias Ochs, Lars Knudsen & Christian Mühlfeld

  3. REBIRTH Cluster of Excellence, Hannover, Germany

    Matthias Ochs, Lars Knudsen, Jan Hegermann, Christoph Wrede, Roman Grothausmann & Christian Mühlfeld

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  1. Matthias Ochs
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  2. Lars Knudsen
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  3. Jan Hegermann
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  4. Christoph Wrede
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Correspondence to Matthias Ochs.

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Dedicated to Detlev Drenckhahn on the occasion of his retirement as Editor-in-Chief of Histochemistry and Cell Biology.

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Ochs, M., Knudsen, L., Hegermann, J. et al. Using electron microscopes to look into the lung. Histochem Cell Biol 146, 695–707 (2016). https://doi.org/10.1007/s00418-016-1502-z

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