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 × 104to 9.9 × 107μm3). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm3of lung tissue to a maximum of 11.1 per mm3of 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.
Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom.
Mark G
MG
Jones
Department of Histopathology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
Aurélie
A
Fabre
μ-VIS X-ray Imaging Centre, Faculty of Engineering and the Environment, University of Southampton, Southampton, United Kingdom.
Philipp
P
Schneider
Clinical Immunology, Department of Medicine, Padua University, Padua, Italy.
Francesco
F
Cinetto
Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom.
Giacomo
G
Sgalla
μ-VIS X-ray Imaging Centre, Faculty of Engineering and the Environment, University of Southampton, Southampton, United Kingdom.
Mark
M
Mavrogordato
Department of Cellular Pathology, University Hospital Southampton, Southampton, United Kingdom.
Sanjay
S
Jogai
Department of Cardiothoracic Surgery, University Hospital Southampton, Southampton, United Kingdom.
Aiman
A
Alzetani
National Institute for Health Research Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom.
Ben G
BG
Marshall
Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Katherine M A
KM
O'Reilly
Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Jane A
JA
Warner
Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Peter M
PM
Lackie
Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
Donna E
DE
Davies
Department of Radiology, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College, London, United Kingdom.
David M
DM
Hansell
Department of Histopathology, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College, London, United Kingdom.
Andrew G
AG
Nicholson
μ-VIS X-ray Imaging Centre, Faculty of Engineering and the Environment, University of Southampton, Southampton, United Kingdom.
Ian
I
Sinclair
Department of Medicine, National Jewish Health, Denver, Colorado, USA.
Kevin K
KK
Brown
Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
Luca
L
Richeldi