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Macrophage expressed tartrate-resistant acid phosphatase 5 promotes pulmonary fibrosis progression

Bergwik, Jesper LU ; Bhongir, Ravi Kiran Varma LU orcid ; Padra, Médea LU ; Adler, Anna LU ; Olm, Franziska LU orcid ; Lång, Pernilla ; Lindstedt, Sandra LU ; Andersson, Göran ; Egesten, Arne LU and Tanner, Lloyd LU (2024) In Immunology p.1-12
Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder involving scarring of pulmonary tissue and a subsequent decrease in respiratory capacity, ultimately resulting in death. Tartrate resistant acid phosphatase 5 (ACP5) plays a role in IPF but the exact mechanisms are yet to be elucidated. In this study, we have utilized various perturbations of the bleomycin mouse model of IPF including genetic knockout, RANKL inhibition, and macrophage adoptive transfer to further understand ACP5's role in pulmonary fibrosis. Genetic ablation of Acp5 decreased immune cell recruitment to the lungs and reduced the levels of hydroxyproline (reflecting extracellular matrix-production) as well as histological damage. Additionally, gene... (More)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder involving scarring of pulmonary tissue and a subsequent decrease in respiratory capacity, ultimately resulting in death. Tartrate resistant acid phosphatase 5 (ACP5) plays a role in IPF but the exact mechanisms are yet to be elucidated. In this study, we have utilized various perturbations of the bleomycin mouse model of IPF including genetic knockout, RANKL inhibition, and macrophage adoptive transfer to further understand ACP5's role in pulmonary fibrosis. Genetic ablation of Acp5 decreased immune cell recruitment to the lungs and reduced the levels of hydroxyproline (reflecting extracellular matrix-production) as well as histological damage. Additionally, gene expression profiling of murine lung tissue revealed downregulation of genes including Ccl13, Mmp13, and Il-1α that encodes proteins specifically related to immune cell recruitment and macrophage/fibroblast interactions. Furthermore, antibody-based neutralization of RANKL, an important inducer of Acp5 expression, reduced immune cell recruitment but did not decrease fibrotic lung development. Adoptive transfer of Acp5
-/- bone marrow-derived monocyte (BMDM) macrophages 7 or 14 days after bleomycin administration resulted in reductions of cytokine production and decreased levels of lung damage, compared to adoptive transfer of WT control macrophages. Taken together, the data presented in this study suggest that macrophage derived ACP5 plays an important role in development of pulmonary fibrosis and could present a tractable target for therapeutic intervention in IPF.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Immunology
pages
1 - 12
publisher
Wiley-Blackwell
external identifiers
  • scopus:85181465728
  • pmid:38178705
ISSN
0019-2805
DOI
10.1111/imm.13748
language
English
LU publication?
yes
additional info
© 2024 The Authors. Immunology published by John Wiley & Sons Ltd.
id
a0d9b7c0-8b05-4c69-9e9c-4f4b2a191ddd
date added to LUP
2024-01-11 09:28:51
date last changed
2024-04-26 23:43:33
@article{a0d9b7c0-8b05-4c69-9e9c-4f4b2a191ddd,
  abstract     = {{<p>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder involving scarring of pulmonary tissue and a subsequent decrease in respiratory capacity, ultimately resulting in death. Tartrate resistant acid phosphatase 5 (ACP5) plays a role in IPF but the exact mechanisms are yet to be elucidated. In this study, we have utilized various perturbations of the bleomycin mouse model of IPF including genetic knockout, RANKL inhibition, and macrophage adoptive transfer to further understand ACP5's role in pulmonary fibrosis. Genetic ablation of Acp5 decreased immune cell recruitment to the lungs and reduced the levels of hydroxyproline (reflecting extracellular matrix-production) as well as histological damage. Additionally, gene expression profiling of murine lung tissue revealed downregulation of genes including Ccl13, Mmp13, and Il-1α that encodes proteins specifically related to immune cell recruitment and macrophage/fibroblast interactions. Furthermore, antibody-based neutralization of RANKL, an important inducer of Acp5 expression, reduced immune cell recruitment but did not decrease fibrotic lung development. Adoptive transfer of Acp5<br>
 -/- bone marrow-derived monocyte (BMDM) macrophages 7 or 14 days after bleomycin administration resulted in reductions of cytokine production and decreased levels of lung damage, compared to adoptive transfer of WT control macrophages. Taken together, the data presented in this study suggest that macrophage derived ACP5 plays an important role in development of pulmonary fibrosis and could present a tractable target for therapeutic intervention in IPF.<br>
 </p>}},
  author       = {{Bergwik, Jesper and Bhongir, Ravi Kiran Varma and Padra, Médea and Adler, Anna and Olm, Franziska and Lång, Pernilla and Lindstedt, Sandra and Andersson, Göran and Egesten, Arne and Tanner, Lloyd}},
  issn         = {{0019-2805}},
  language     = {{eng}},
  month        = {{01}},
  pages        = {{1--12}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Immunology}},
  title        = {{Macrophage expressed tartrate-resistant acid phosphatase 5 promotes pulmonary fibrosis progression}},
  url          = {{http://dx.doi.org/10.1111/imm.13748}},
  doi          = {{10.1111/imm.13748}},
  year         = {{2024}},
}