Using electron microscopes to look into the lung.
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.
Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. ochs.matthias@mh-hannover.de.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany. ochs.matthias@mh-hannover.de.|REBIRTH Cluster of Excellence, Hannover, Germany. ochs.matthias@mh-hannover.de.
Matthias
M
Ochs
Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.|REBIRTH Cluster of Excellence, Hannover, Germany.
Lars
L
Knudsen
Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|REBIRTH Cluster of Excellence, Hannover, Germany.
Jan
J
Hegermann
Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|REBIRTH Cluster of Excellence, Hannover, Germany.
Christoph
C
Wrede
Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|REBIRTH Cluster of Excellence, Hannover, Germany.
Roman
R
Grothausmann
Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.|REBIRTH Cluster of Excellence, Hannover, Germany.
Christian
C
Mühlfeld
D000818:Animals; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000648:ultrastructure*; D008854:Microscopy, Electron
Collapse induration; Electron microscopy; Fibrosis; Stereology; Surfactant; Type II alveolar epithelial cell; Volume EM
Science. 1962 Aug 24;137(3530):577-85
14005590
Cell Tissue Res. 1980;209(2):201-16
6994890
Histochem Cell Biol. 1996 Jul;106(1):41-58
8858366
Am J Physiol Lung Cell Mol Physiol. 2013 Aug 1;305(3):L205-21
23709622
Acta Anat (Basel). 1971;78(3):425-43
4995841
Front Neuroanat. 2009 Oct 05;3:18
19949485
Respir Physiol. 1968 Jan;4(1):42-57
4867416
Am Rev Respir Dis. 1977 Jun;115(6 Pt 2):81-91
326115
Anat Rec. 2001 Jun 1;263(2):118-26
11360229
Am J Physiol Lung Cell Mol Physiol. 2015 Dec 1;309(11):L1286-93
26432874
J Cell Biol. 1964 Oct;23:101-12
14228505
Part Fibre Toxicol. 2015 Oct 31;12:35
26521139
Annu Rev Pathol. 2015;10:371-93
25621661
J Cell Biol. 2013 Aug 5;202(3):407-19
23918936
N Engl J Med. 2001 Aug 16;345(7):517-25
11519507
Cell Tissue Res. 2015 Apr;360(1):43-59
25403623
Physiol Rev. 1973 Apr;53(2):419-95
4581654
Annu Rev Physiol. 1997;59:1-21
9074754
Nat Rev Mol Cell Biol. 2003 Sep;Suppl:SS6-10
14587520
J Struct Biol. 2007 Sep;159(3):443-50
17606383
Science. 2001 Feb 16;291(5507):1363-5
11233453
Expert Rev Respir Med. 2015 Aug;9(4):411-8
26165208
J Histochem Cytochem. 1981 May;29(5):663-71
6166664
Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418
20130146
Hum Pathol. 1985 Oct;16(10):1015-24
4043950
Anat Rec. 1952 Aug;113(4):437-49
14943972
Histochem Cell Biol. 2010 Oct;134(4):319-26
20809233
Ann Intern Med. 2001 Jan 16;134(2):136-51
11177318
J Heart Lung Transplant. 2010 Mar;29(3):327-34
19783172
Am J Respir Cell Mol Biol. 2004 Apr;30(4):449-58
12972403
Am J Respir Cell Mol Biol. 2002 Jun;26(6):659-70
12034564
Ann Anat. 2009 Jun;191(3):231-47
19264467
Ultramicroscopy. 1988;24(2-3):251-68
3281358
J Microsc. 2013 Nov;252(2):93-9
24111814
Radiology. 2010 Jun;255 (3):692-706
20501710
Microsc Res Tech. 1993 Dec 1;26(5):366-73
8286782
Am J Physiol Lung Cell Mol Physiol. 2016 Mar 1;310(5):L387-92
26684253
Radiology. 2008 Mar;246(3):697-722
18195376
Anat Rec A Discov Mol Cell Evol Biol. 2005 Oct;286(2):885-90
16086431
Front Neural Circuits. 2014 Jun 27;8:68
25018701
J Histochem Cytochem. 1978 Dec;26(12):1074-81
366014
J Microsc. 2006 Jun;222(Pt 3):188-200
16872418
Cell Physiol Biochem. 2010;25(1):27-40
20054142
Curr Opin Struct Biol. 2002 Oct;12(5):679-84
12464323
Eur Respir Rev. 2012 Jun 1;21(124):152-60
22654088
AJR Am J Roentgenol. 1979 Dec;133(6):1021-31
116490
J Microsc. 2015 Aug;259(2):155-64
26139222
Am J Physiol. 1990 Oct;259(4 Pt 1):L159-84
2221080
Am Rev Respir Dis. 1989 Aug;140(2):513-24
2669580
Eur Respir J. 2000 Mar;15(3):526-31
10759447
N Engl J Med. 2000 May 4;342(18):1334-49
10793167
Histochem Cell Biol. 2008 Nov;130(5):877-89
18795316
J Anat. 2015 Apr;226(4):309-21
25753334
Am J Respir Crit Care Med. 2004 Jan 1;169(1):120-4
14512270
Am J Respir Crit Care Med. 2006 Sep 15;174(6):654-8
16799077
Eur Respir J. 2009 Mar;33(3):625-33
19010995
Am J Respir Cell Mol Biol. 2002 Jan;26(1):91-8
11751208
Respir Physiol. 1969 Dec;8(1):13-36
4904279
Am Rev Respir Dis. 1980 Aug;122(2):289-301
7416606
Am J Physiol Lung Cell Mol Physiol. 2015 Sep 15;309(6):L526-36
26186944
Virchows Arch B Cell Pathol Incl Mol Pathol. 1989;58(1):1-13
2574513
Curr Opin Neurobiol. 2012 Feb;22(1):154-61
22119321
EMBO J. 2004 Sep 15;23(18):3583-8
15318169
Nat Protoc. 2012 Jan 12;7(2):193-206
22240582
Micron. 2014 Jun;61:9-19
24792442
Am J Physiol Lung Cell Mol Physiol. 2013 Sep 15;305(6):L405-8
23851316
J Histochem Cytochem. 1994 Jun;42(6):805-9
8189041
Hum Pathol. 1986 Sep;17(9):971-3
3759081
Compr Physiol. 2016 Mar 15;6(2):827-95
27065169
J Cell Sci. 2013 Oct 15;126(Pt 20):4545-52
24124192
Trends Cell Biol. 2015 Feb;25(2):59-64
25455351
Am J Physiol Lung Cell Mol Physiol. 2004 Dec;287(6):L1333-41
15310555
Respir Res. 2007 Oct 03;8:70
17915009
Am J Physiol Lung Cell Mol Physiol. 2013 Jul 1;305(1):L15-22
23624789
Am Rev Respir Dis. 1977 Oct;116(4):589-615
921049
Methods Cell Biol. 1989;31:513-51
2674631
Histochem Cell Biol. 2008 Aug;130(2):185-96
18566823
Anat Rec A Discov Mol Cell Evol Biol. 2004 Apr;277(2):287-97
15052656
Am J Physiol Lung Cell Mol Physiol. 2013 Dec;305(12):L906-11
24142519
Anat Rec. 1953 Oct;117(2):241-63
13104990
Histochem Cell Biol. 2008 Aug;130(2):299-313
18553098
Am J Respir Crit Care Med. 1999 Aug;160(2):718-24
10430751
Respir Res. 2001;2(1):33-46
11686863
Am J Physiol Lung Cell Mol Physiol. 2015 Sep 15;309(6):L507-25
26186947
J Histochem Cytochem. 1980 Feb;28(2):149-60
7354212
Arch Pathol Lab Med. 2012 Jun;136(6):591-600
22136526
Histochem Cell Biol. 2014 Oct;142(4):347-60
25151300
J Appl Physiol (1985). 2007 Jan;102(1):459-67
16973815
Am J Respir Cell Mol Biol. 2015 Feb;52(2):232-43
25033427
Anat Rec (Hoboken). 2009 Feb;292(2):183-9
19177340
AJR Am J Roentgenol. 1991 Feb;156(2):225-33
1898791
Chest. 1988 Dec;94(6):1309-11
3191777
Proc Soc Exp Biol Med. 1957 May;95(1):170-2
13432025
Histochem Cell Biol. 1996 Jul;106(1):1-8
8858362
JCI Insight. 2016 Apr 21;1(5):null
27275013
Nat Rev Mol Cell Biol. 2006 Mar;7(3):225-30
16482091
Trends Cell Biol. 2005 Jan;15(1):43-51
15653077
Part Fibre Toxicol. 2007 Nov 12;4:11
17996124
J Biol Chem. 2003 Dec 5;278(49):49006-14
13129928
Annu Rev Pathol. 2011;6:147-63
20936936
Am Rev Respir Dis. 1977 Oct;116(4):637-47
921050
Z Zellforsch Mikrosk Anat. 1966;69:418-27
5973105
Ann Anat. 2009 Apr;191(2):153-70
19135344
Exp Lung Res. 2015 Mar;41(2):57-73
25514507
J Microsc. 2001 Sep;203(Pt 3):285-94
11555146
Bone. 1993 May-Jun;14(3):217-22
8363860
Am J Respir Crit Care Med. 1997 May;155(5):1649-56
9154871
Curr Opin Struct Biol. 2013 Oct;23(5):771-7
24090931
Neuron. 2007 Jul 5;55(1):25-36
17610815
J Microsc. 2012 Mar;245(3):221-4
22457877
Nat Methods. 2016 Jan;13(1):19-22
27110630
J Microsc. 1984 May;134(Pt 2):127-36
6737468
Am J Respir Crit Care Med. 2015 Mar 1;191(5):504-13
25723823