ß1 Integrin regulates adult lung alveolar epithelial cell inflammation.
JCI Insight
; 5(2)2020 01 30.
Article
em En
| MEDLINE
| ID: mdl-31873073
ABSTRACT
Integrins, the extracellular matrix receptors that facilitate cell adhesion and migration, are necessary for organ morphogenesis; however, their role in maintaining adult tissue homeostasis is poorly understood. To define the functional importance of ß1 integrin in adult mouse lung, we deleted it after completion of development in type 2 alveolar epithelial cells (AECs). Aged ß1 integrin-deficient mice exhibited chronic obstructive pulmonary disease-like (COPD-like) pathology characterized by emphysema, lymphoid aggregates, and increased macrophage infiltration. These histopathological abnormalities were preceded by ß1 integrin-deficient AEC dysfunction such as excessive ROS production and upregulation of NF-κB-dependent chemokines, including CCL2. Genetic deletion of the CCL2 receptor, Ccr2, in mice with ß1 integrin-deficient type 2 AECs impaired recruitment of monocyte-derived macrophages and resulted in accelerated inflammation and severe premature emphysematous destruction. The lungs exhibited reduced AEC efferocytosis and excessive numbers of inflamed type 2 AECs, demonstrating the requirement for recruited monocytes/macrophages in limiting lung injury and remodeling in the setting of a chronically inflamed epithelium. These studies support a critical role for ß1 integrin in alveolar homeostasis in the adult lung.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Integrina beta1
/
Células Epiteliais Alveolares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2020
Tipo de documento:
Article