Interstitial pneumonia induced by bleomycin treatment is exacerbated in Angptl2-deficient mice.

Abstract

Angiopoietin-like protein 2 (ANGPTL2) is a chronic inflammatory mediator that, when deregulated, is associated with various pathologies. However, little is known about its activity in lung. To assess a possible lung function, we generated a rabbit monoclonal antibody that specifically recognizes mouse ANGPTL2 and then evaluated protein expression in mouse lung tissue. We observed abundant ANGPTL2 expression in both alveolar epithelial type I and type II cells and in resident alveolar macrophages under normal conditions. To assess ANGPTL2 function, we compared lung phenotypes in Angptl2 knockout (KO) and wild-type mice but observed no overt changes. We then generated a bleomycin-induced interstitial pneumonia model using wild-type and Angptl2 KO mice. Bleomycin-treated wild-type mice showed specifically upregulated ANGPTL2 expression in areas of severe fibrosing interstitial pneumonia, while Angptl2 KO mice developed more severe lung fibrosis than did comparably treated wild-type mice. Lung fibrosis seen following bone marrow transplant was comparable in wild-type or Angptl2 KO mice treated with bleomycin, suggesting that Angptl2 loss in myeloid cells does not underlie fibrotic phenotypes. We conclude that Angptl2 deficiency in lung epithelial cells and resident alveolar macrophages causes severe lung fibrosis seen following bleomycin treatment, suggesting that ANGPTL2 derived from these cell types plays a protective role against fibrosis in lung.

• Authors: Ikuyo Motokawa, Motoyoshi Endo, Kazutoyo Terada, Haruki Horiguchi, Keishi Miyata, Tsuyoshi Kadomatsu, Jun Morinaga, Taichi Sugizaki, Takaaki Ito, Kimi Araki, Masaki Suimye Morioka, Ichiro Manabe, Takuya Samukawa, Masaki Watanabe, Hiromasa Inoue, Yuichi Oike
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 311 Issue 4 Pg. L704-L713 (Oct 01 2016) ISSN: 1522-1504 [Electronic] United States
• PMID: 27542805 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 the American Physiological Society.

Chemical References

• Angiopoietin-Like Protein 2
• Angiopoietin-like Proteins
• Angiopoietins
• Angptl2 protein, mouse
• Thrombospondin 1
• Thbs1 protein, mouse
• Bleomycin

Topics

• 3T3-L1 Cells
• Alveolar Epithelial Cells (metabolism)
• Angiopoietin-Like Protein 2
• Angiopoietin-like Proteins
• Angiopoietins (genetics, metabolism)
• Animals
• Bleomycin
• Lung (pathology)
• Lung Diseases, Interstitial (chemically induced, genetics, pathology)
• Macrophages, Alveolar (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Cells (metabolism)
• Pulmonary Fibrosis (chemically induced, genetics, pathology)
• Thrombospondin 1 (genetics, metabolism)