Beta-2-microglobulin
negative regulation of epithelial cell proliferation
β<sub>2</sub>-Microglobulin participates in development of lung emphysema by inducing lung epithelial cell senescence.
β<sub>2</sub>-Microglobulin (β<sub>2</sub>M), 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 β<sub>2</sub>M in the development of lung emphysema. Here, we found that concentrations of β<sub>2</sub>M 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, <i>P</i> < 0.01). Moreover, the expression of β<sub>2</sub>M was significantly higher in lung tissue of emphysema (39.90 ± 1.97 vs. 23.94 ± 2.11%, <i>P</i> < 0.01). Immunofluorescence showed that β<sub>2</sub>M was mainly expressed in prosurfactant protein C-positive (pro-SPC<sup>+</sup>) alveolar epithelial cells and CD14<sup>+</sup> macrophages. Exposure to recombinant human β<sub>2</sub>M 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-β<sub>2</sub>M antibody. However, anti-β<sub>2</sub>M 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 β<sub>2</sub>M, and the hemochromatosis gene (HFE) protein was observed on A549 cells. These data suggest β<sub>2</sub>M might participate in the development of lung emphysema through induction of lung epithelial cell senescence and inhibition.