Regulatory effects of beta-2-microglobulin on reactive oxygen species generation in polymorphonuclear cells

Beta-2-microglobulin (β2m) constitutes the invariant light chain of the major histocompatibility complex class I (MHC I) and is therefore expressed on all nucleated cells. Soluble β2m is present in biological fluids, platelets and neutrophil granules. Immune and epithelial cells can upregulate the production and secretion of β2m in response to pro-inflammatory cytokines. In the present study, we investigated the effects of exogenous β2m and two proteolytically processed forms, cK58β2m and dK58β2m, on reactive oxygen species (ROS) production in polymorphonuclear leukocytes (PMNs). β2m was shown to enhance ROS generation triggered by latex beads, while cK58β2m and dK58β2m suppressed both baseline ROS levels and responses to latex beads, TNF-α, and fMLF. The inhibitory effect of cK58β2m and dK58β2m was also confirmed in DMSO-differentiated HL-60 cells, a neutrophil-like cell line. Furthermore, treatment with dK58β2m impaired the recruitment of p47phox and p67phox to the plasma membrane following fMLF stimulation, two key subunits of the NADPH oxidase complex responsible for superoxide anion production in neutrophils. This may explain the reduced ROS production observed in cells treated with dK58β2m. These results highlight a potential role for β2m, cK58β2m, and dK58β2m in modulating the innate immune response through control of ROS production in PMNs.