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- Title
Neutrophil extracellular traps are involved in the occurrence of interstitial lung disease in a murine experimental autoimmune myositis model.
- Authors
Bai, Ling; Zhu, Jiarui; Ma, Wenlan; Li, Feifei; Zhao, Peipei; Zhang, Sigong
- Abstract
The excessive formation of neutrophil extracellular traps (NETs) has been demonstrated to be a pathogenic mechanism of idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD). This study aimed to answer whether an experimental autoimmune myositis (EAM) model can be used to study IIM-ILD and whether NETs participate in the development of EAM-ILD. An EAM mouse model was established using skeletal muscle homogenate and pertussis toxin (PTX). The relationship between NETs and the ILD phenotype was determined via histopathological analysis. As NETs markers, serum cell-free DNA (cfDNA) and serum citrullinated histone 3 (Cit-H3)-DNA were tested. The healthy mouse was injected with PTX intraperitoneally to determine whether PTX intervention could induce NETs formation in vivo. Neutrophils isolated from the peripheral blood of healthy individuals were given different interventions to determine whether PTX and skeletal muscle homogenate can induce neutrophils to form NETs in vitro. EAM-ILD had three pathological phenotypes similar to IIM-ILD. Cit-H3, neutrophil myeloperoxidase, and neutrophil elastase were overexpressed in the lungs of EAM model mice. The serum cfDNA level and Cit-H3-DNA complex level were significantly increased in EAM model mice. Serum cfDNA levels were increased significantly in vivo intervention with PTX in mice. Both PTX and skeletal muscle homogenate-induced neutrophils to form NETs in vitro. EAM-ILD pathological phenotypes are similar to IIM-ILD, and NETs are involved in the development of ILD in a murine model of EAM. Thus, the EAM mouse model can be used as an ideal model targeting NETs to prevent and treat IIM-ILD. A murine model of experimental autoimmune myositis induced by skeletal muscle homogenate and pertussis toxin suffered from interstitial lung disease similar to idiopathic inflammatory myopathy-associated interstitial lung disease. NETs are involved in the occurrence of interstitial lung disease in the model. Graphical Abstract
- Subjects
MYOSITIS; INTERSTITIAL lung diseases; LEUCOCYTE elastase; PERTUSSIS toxin; NEUTROPHILS; IDIOPATHIC diseases; CELL-free DNA
- Publication
Clinical & Experimental Immunology, 2024, Vol 215, Issue 2, p126
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1093/cei/uxad104