title: β2-Microglobulin participates in development of lung emphysema by inducing lung epithelial cell senescence.
abstract: β2-Microglobulin (β2M), the light chain of the major histocompatibility complex class I (MHC I), has been identified as a proaging factor and is involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of β2M in the development of lung emphysema. Here, we found that concentrations of β2M in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 ± 0.12 vs. 1.42 ± 0.06 mg/l,P< 0.01). Moreover, the expression of β2M was significantly higher in lung tissue of emphysema (39.90 ± 1.97 vs. 23.94 ± 2.11%,P< 0.01). Immunofluorescence showed that β2M was mainly expressed in prosurfactant protein C-positive (pro-SPC+) alveolar epithelial cells and CD14+macrophages. Exposure to recombinant human β2M and cigarette smoke extract (CSE) in vitro enhanced cellular senescence and inhibited proliferation of A549 cells, which was partially reversed by the presence of anti-β2M antibody. However, anti-β2M antibody did not attenuate the elevated production of IL-1β, IL-6, and TNF-α in A549 cells that were exposed to CSE. Immunofluorescence showed that colocalization of β2M, and the hemochromatosis gene (HFE) protein was observed on A549 cells. These data suggest β2M might participate in the development of lung emphysema through induction of lung epithelial cell senescence and inhibition.
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.|Beijing Institute of Respiratory Medicine, Beijing, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.|Beijing Institute of Respiratory Medicine, Beijing, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Center for Basic Medical Research, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Zheng
authors.affiliation: Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Gao
authors.affiliation: Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China; and.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.|Department of Immunology, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.|Beijing Institute of Respiratory Medicine, Beijing, People's Republic of China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Fu
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.|Beijing Institute of Respiratory Medicine, Beijing, People's Republic of China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Xu
authors.affiliation: Department of Immunology, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Immunology, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Sun
authors.initials: S
authors.lastname: Ying
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China; kewuhuang@126.com.|Beijing Institute of Respiratory Medicine, Beijing, People's Republic of China.
authors.forename: Kewu
authors.initials: K
authors.lastname: Huang
mesh_terms: D000072283:A549 Cells; D000906:Antibodies / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D003710:Demography; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011656:Pulmonary Emphysema / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D012907:Smoking / Q000009:adverse effects; D001613:beta 2-Microglobulin / Q000097:blood / Q000378:metabolism*
chemical_list: D000906:Antibodies; D001613:beta 2-Microglobulin
keywords: CSE; emphysema; epithelial cells; senescence; β2-microglobulin