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Three-dimensional characterization of fibroblast foci in idiopathic pulmonary fibrosis

Three-dimensional characterization of fibroblast foci in idiopathic pulmonary fibrosis
Three-dimensional characterization of fibroblast foci in idiopathic pulmonary fibrosis

In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, fibroblast foci are considered small, distinct lesions, although they have been proposed to form a highly interconnected reticulum as the leading edge of a "wave" of fibrosis. Here, we characterized fibroblast focus morphology and interrelationships in 3D using an integrated micro-CT and histological methodology. In 3D, fibroblast foci were morphologically complex structures, with large variations in shape and volume (range, 1.3 × 10(4) to 9.9 × 10(7) μm(3)). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm(3) of lung tissue to a maximum of 11.1 per mm(3) of lung tissue. Each focus was an independent structure, and no interconnections were observed. Together, our data indicate that in 3D fibroblast foci form a constellation of heterogeneous structures with large variations in shape and volume, suggesting previously unrecognized plasticity. No evidence of interconnectivity was identified, consistent with the concept that foci represent discrete sites of lung injury and repair.

2379-3708
Jones, Mark G.
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Fabre, Aurélie
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Schneider, Philipp
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Cinetto, Francesco
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Sgalla, Giacomo
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Mavrogordato, Mark
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Jogai, Sanjay
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Alzetani, Aiman
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Marshall, Ben G.
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O'Reilly, Katherine M.A.
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Warner, Jane A.
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Lackie, Peter M.
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Davies, Donna E.
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Hansell, David M.
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Nicholson, Andrew G.
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Sinclair, Ian
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Brown, Kevin K.
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Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
Jones, Mark G.
a6fd492e-058e-4e84-a486-34c6035429c1
Fabre, Aurélie
ec28c2e8-8666-40a3-904e-77b4e2b2d0cd
Schneider, Philipp
a810f925-4808-44e4-8a4a-a51586f9d7ad
Cinetto, Francesco
a45e3e6e-2bf1-40b6-a51f-251cec4060ed
Sgalla, Giacomo
f7c37658-a00c-4b08-8dea-fa90b279de79
Mavrogordato, Mark
f3e0879b-118a-463a-a130-1c890e9ab547
Jogai, Sanjay
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Alzetani, Aiman
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Marshall, Ben G.
12be7650-0780-4923-8c8d-e26862fe3213
O'Reilly, Katherine M.A.
6c323cd0-0c68-4913-9666-7e4f655b816f
Warner, Jane A.
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Lackie, Peter M.
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a
Davies, Donna E.
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Hansell, David M.
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Nicholson, Andrew G.
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Sinclair, Ian
6005f6c1-f478-434e-a52d-d310c18ade0d
Brown, Kevin K.
3448c3ff-89a1-4cba-ab95-97bc178b6450
Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26

Jones, Mark G., Fabre, Aurélie, Schneider, Philipp, Cinetto, Francesco, Sgalla, Giacomo, Mavrogordato, Mark, Jogai, Sanjay, Alzetani, Aiman, Marshall, Ben G., O'Reilly, Katherine M.A., Warner, Jane A., Lackie, Peter M., Davies, Donna E., Hansell, David M., Nicholson, Andrew G., Sinclair, Ian, Brown, Kevin K. and Richeldi, Luca (2016) Three-dimensional characterization of fibroblast foci in idiopathic pulmonary fibrosis. JCI Insight, 1 (5). (doi:10.1172/jci.insight.86375).

Record type: Article

Abstract

In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, fibroblast foci are considered small, distinct lesions, although they have been proposed to form a highly interconnected reticulum as the leading edge of a "wave" of fibrosis. Here, we characterized fibroblast focus morphology and interrelationships in 3D using an integrated micro-CT and histological methodology. In 3D, fibroblast foci were morphologically complex structures, with large variations in shape and volume (range, 1.3 × 10(4) to 9.9 × 10(7) μm(3)). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm(3) of lung tissue to a maximum of 11.1 per mm(3) of lung tissue. Each focus was an independent structure, and no interconnections were observed. Together, our data indicate that in 3D fibroblast foci form a constellation of heterogeneous structures with large variations in shape and volume, suggesting previously unrecognized plasticity. No evidence of interconnectivity was identified, consistent with the concept that foci represent discrete sites of lung injury and repair.

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Accepted/In Press date: 15 March 2016
e-pub ahead of print date: 21 April 2016
Published date: 21 April 2016
Organisations: NIHR Southampton Respiratory Biomedical Research Unit, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 392629
URI: https://eprints.soton.ac.uk/id/eprint/392629
ISSN: 2379-3708
PURE UUID: fa44b107-d589-48fd-8f67-54dd48eb1b05
ORCID for Philipp Schneider: ORCID iD orcid.org/0000-0001-7499-3576
ORCID for Peter M. Lackie: ORCID iD orcid.org/0000-0001-7138-3764
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 22 Apr 2016 08:36
Last modified: 28 Nov 2019 01:40

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Contributors

Author: Mark G. Jones
Author: Aurélie Fabre
Author: Francesco Cinetto
Author: Giacomo Sgalla
Author: Sanjay Jogai
Author: Aiman Alzetani
Author: Ben G. Marshall
Author: Katherine M.A. O'Reilly
Author: Jane A. Warner
Author: Peter M. Lackie ORCID iD
Author: Donna E. Davies ORCID iD
Author: David M. Hansell
Author: Andrew G. Nicholson
Author: Ian Sinclair
Author: Kevin K. Brown
Author: Luca Richeldi

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