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.

Keywords: CSE; emphysema; epithelial cells; senescence; β2-microglobulin.