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Extracellular matrix alterations and acute inflammation; developing in parallel during early induction of pulmonary fibrosis.

Rydell-Törmänen, Kristina LU ; Andréasson, Kristofer LU ; Hesselstrand, Roger LU ; Risteli, Juha; Heinegård, Dick LU ; Saxne, Tore LU and Westergren-Thorsson, Gunilla LU (2012) In Laboratory Investigation 92(6). p.917-925
Abstract
Pulmonary fibrosis is a hallmark of several systemic diseases such as systemic sclerosis. Initiation and early development is not well characterized, as initiation usually is unnoticed in patients, yet fibrosis has been considered a late event, occurring after an inflammatory phase. By utilizing an animal model, the starting point can be defined and the initiation process and early development thoroughly investigated. To investigate these processes from a systemic perspective, we choose a systemic administration route, instead of the more commonly used local administration. The aim of this work was to study the initiation of pulmonary fibrosis in an animal model and to investigate early alterations in connective tissue, cell turnover and... (More)
Pulmonary fibrosis is a hallmark of several systemic diseases such as systemic sclerosis. Initiation and early development is not well characterized, as initiation usually is unnoticed in patients, yet fibrosis has been considered a late event, occurring after an inflammatory phase. By utilizing an animal model, the starting point can be defined and the initiation process and early development thoroughly investigated. To investigate these processes from a systemic perspective, we choose a systemic administration route, instead of the more commonly used local administration. The aim of this work was to study the initiation of pulmonary fibrosis in an animal model and to investigate early alterations in connective tissue, cell turnover and acute immune response in lung parenchyma. Animals were injected subcutaneously with bleomycin, three times a week (w) for 1-4w (controls received saline). Total collagen was histologically assessed by Picro Sirius Red and Masson's Trichrome, collagen production by antibodies directed against N-terminal of procollagens I and III, proliferation by labeling with proliferating cell nuclear antigen, apoptosis by TUNEL and innate immunity by detecting neutrophils and macrophages. Total collagen was significantly increased at 1, 2 and 4w compared with controls. Procollagen I, was increased at 1w and remained increased, whereas procollagen III-staining was increased at 2w, compared with controls. Myofibroblasts were increased at all times as were proliferation, whereas apoptosis was increased from 2w. Neutrophils peaked at 1w (2779±820 cells/mm(2)) and gradually decreased, whereas macrophages peaked at 2w (135±29 cells/mm(2)). Subcutaneously administered bleomycin induces rapid alterations in connective tissue and cell turnover, suggesting a plasticity of the connective tissue. A transient neutrophilia is detected and increased number of macrophages likely represents a clearance process of said neutrophils. The study suggests fibrosis initiation and acute inflammation to occur in parallel in this model.Laboratory Investigation advance online publication, 2 April 2012; doi:10.1038/labinvest.2012.57. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Laboratory Investigation
volume
92
issue
6
pages
917 - 925
publisher
Nature Publishing Group
external identifiers
  • wos:000304730600010
  • pmid:22469699
  • scopus:84861609107
ISSN
1530-0307
DOI
10.1038/labinvest.2012.57
language
English
LU publication?
yes
id
eece2ec8-af19-4889-9d62-2d9900d242d7 (old id 2519920)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22469699?dopt=Abstract
date added to LUP
2012-05-06 13:54:38
date last changed
2017-10-01 04:55:59
@article{eece2ec8-af19-4889-9d62-2d9900d242d7,
  abstract     = {Pulmonary fibrosis is a hallmark of several systemic diseases such as systemic sclerosis. Initiation and early development is not well characterized, as initiation usually is unnoticed in patients, yet fibrosis has been considered a late event, occurring after an inflammatory phase. By utilizing an animal model, the starting point can be defined and the initiation process and early development thoroughly investigated. To investigate these processes from a systemic perspective, we choose a systemic administration route, instead of the more commonly used local administration. The aim of this work was to study the initiation of pulmonary fibrosis in an animal model and to investigate early alterations in connective tissue, cell turnover and acute immune response in lung parenchyma. Animals were injected subcutaneously with bleomycin, three times a week (w) for 1-4w (controls received saline). Total collagen was histologically assessed by Picro Sirius Red and Masson's Trichrome, collagen production by antibodies directed against N-terminal of procollagens I and III, proliferation by labeling with proliferating cell nuclear antigen, apoptosis by TUNEL and innate immunity by detecting neutrophils and macrophages. Total collagen was significantly increased at 1, 2 and 4w compared with controls. Procollagen I, was increased at 1w and remained increased, whereas procollagen III-staining was increased at 2w, compared with controls. Myofibroblasts were increased at all times as were proliferation, whereas apoptosis was increased from 2w. Neutrophils peaked at 1w (2779±820 cells/mm(2)) and gradually decreased, whereas macrophages peaked at 2w (135±29 cells/mm(2)). Subcutaneously administered bleomycin induces rapid alterations in connective tissue and cell turnover, suggesting a plasticity of the connective tissue. A transient neutrophilia is detected and increased number of macrophages likely represents a clearance process of said neutrophils. The study suggests fibrosis initiation and acute inflammation to occur in parallel in this model.Laboratory Investigation advance online publication, 2 April 2012; doi:10.1038/labinvest.2012.57.},
  author       = {Rydell-Törmänen, Kristina and Andréasson, Kristofer and Hesselstrand, Roger and Risteli, Juha and Heinegård, Dick and Saxne, Tore and Westergren-Thorsson, Gunilla},
  issn         = {1530-0307},
  language     = {eng},
  number       = {6},
  pages        = {917--925},
  publisher    = {Nature Publishing Group},
  series       = {Laboratory Investigation},
  title        = {Extracellular matrix alterations and acute inflammation; developing in parallel during early induction of pulmonary fibrosis.},
  url          = {http://dx.doi.org/10.1038/labinvest.2012.57},
  volume       = {92},
  year         = {2012},
}