A novel murine model of pulmonary fibrosis: the role of platelets in chronic changes induced by bleomycin

R. Carrington; S. Jordan; Y. J. Wong; S. C. Pitchford; C. P. Page

doi:10.1016/j.vascn.2021.107057

A novel murine model of pulmonary fibrosis: the role of platelets in chronic changes induced by bleomycin

R. Carrington^*, S. Jordan, Y. J. Wong, S. C. Pitchford, C. P. Page

^*Corresponding author for this work

Covance Laboratories Ltd

Research output: Contribution to journal › Article › peer-review

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and destruction of lung tissue that is ultimately fatal. There is a need to develop improved treatments for IPF. One problem with identifying novel treatments of IPF is the poor predictability of current preclinical models. Few model investigate lung function changes, rather relying on histological changes which doesn't adequately reflect the complete clinical situation. The aim of this study was to establish a novel model of pulmonary fibrosis where we could investigate changes in lung function, and histology. We have also utilised this model to investigate the role of platelets in pulmonary fibrosis as platelets have been recognised as having a broader role than just facilitating haemostasis. Lung fibrosis was induced in male C57BL6/J mice by intranasal bleomycin on Days 0, 1, 2, 5, 6 and 7. Platelets were depleted by twice-weekly administration of anti-platelet antibodies. On Day 35 mice were assessed by examining lung function, platelet infiltration into lung tissues and bronchoalveolar lavage fluid (BAL), levels of BAL Tissue growth factor (TGF)-β levels, and the degree of fibrosis evaluated histologically. Repeated bleomycin administration caused loss of lung function associated with fibrosis assessed histologically. Platelet depletion resulted in a reduction in fibrosis and modest inhibition of lung function changes. We have established a novel model of pulmonary fibrosis that is associated with a decline in lung function similar to the clinical setting. Furthermore, platelet depletion resulted in a less severe fibrosis suggesting that targeting platelets maybe worth further investigation.

Original language	English
Article number	107057
Journal	Journal of pharmacological and toxicological methods
Volume	109
Early online date	2 May 2021
DOIs	https://doi.org/10.1016/j.vascn.2021.107057
Publication status	E-pub ahead of print - 2 May 2021

Keywords

Animal models
IPF
Platelets

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10.1016/j.vascn.2021.107057

A novel murine model_CARRINGTON_Accepted30March2021Publishedonline2May2021_GREEN AAM (CC BY-NC-ND)Accepted author manuscript, 575 KBLicence: CC BY-NC-ND

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abstract = "Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and destruction of lung tissue that is ultimately fatal. There is a need to develop improved treatments for IPF. One problem with identifying novel treatments of IPF is the poor predictability of current preclinical models. Few model investigate lung function changes, rather relying on histological changes which doesn't adequately reflect the complete clinical situation. The aim of this study was to establish a novel model of pulmonary fibrosis where we could investigate changes in lung function, and histology. We have also utilised this model to investigate the role of platelets in pulmonary fibrosis as platelets have been recognised as having a broader role than just facilitating haemostasis. Lung fibrosis was induced in male C57BL6/J mice by intranasal bleomycin on Days 0, 1, 2, 5, 6 and 7. Platelets were depleted by twice-weekly administration of anti-platelet antibodies. On Day 35 mice were assessed by examining lung function, platelet infiltration into lung tissues and bronchoalveolar lavage fluid (BAL), levels of BAL Tissue growth factor (TGF)-β levels, and the degree of fibrosis evaluated histologically. Repeated bleomycin administration caused loss of lung function associated with fibrosis assessed histologically. Platelet depletion resulted in a reduction in fibrosis and modest inhibition of lung function changes. We have established a novel model of pulmonary fibrosis that is associated with a decline in lung function similar to the clinical setting. Furthermore, platelet depletion resulted in a less severe fibrosis suggesting that targeting platelets maybe worth further investigation.",

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AB - Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and destruction of lung tissue that is ultimately fatal. There is a need to develop improved treatments for IPF. One problem with identifying novel treatments of IPF is the poor predictability of current preclinical models. Few model investigate lung function changes, rather relying on histological changes which doesn't adequately reflect the complete clinical situation. The aim of this study was to establish a novel model of pulmonary fibrosis where we could investigate changes in lung function, and histology. We have also utilised this model to investigate the role of platelets in pulmonary fibrosis as platelets have been recognised as having a broader role than just facilitating haemostasis. Lung fibrosis was induced in male C57BL6/J mice by intranasal bleomycin on Days 0, 1, 2, 5, 6 and 7. Platelets were depleted by twice-weekly administration of anti-platelet antibodies. On Day 35 mice were assessed by examining lung function, platelet infiltration into lung tissues and bronchoalveolar lavage fluid (BAL), levels of BAL Tissue growth factor (TGF)-β levels, and the degree of fibrosis evaluated histologically. Repeated bleomycin administration caused loss of lung function associated with fibrosis assessed histologically. Platelet depletion resulted in a reduction in fibrosis and modest inhibition of lung function changes. We have established a novel model of pulmonary fibrosis that is associated with a decline in lung function similar to the clinical setting. Furthermore, platelet depletion resulted in a less severe fibrosis suggesting that targeting platelets maybe worth further investigation.

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A novel murine model of pulmonary fibrosis: the role of platelets in chronic changes induced by bleomycin

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