Beta-2-microglobulin synthesis is increased during activation of human monocytes

We have investigated the regulation of beta 2-microglobulin (beta 2-M) synthesis by monocytes. Recent interest in beta 2-M has developed since the discovery that this protein forms amyloid fibrils in patients undergoing long-term, chronic hemodialysis. The beta 2-M amyloidosis is linked to the greatly elevated levels of monomeric beta 2-M in their circulation. Since factors that govern beta 2-M release from plasma membranes are not known, we endeavored to evaluate beta 2-M release during monocyte activation. Utilizing a human monocyte-like cell line, U937, we studied the effect of bacterial toxin stimulation on levels of membrane, cell surface, and supernatant beta 2-M. We now present a novel method to purify beta 2-M, a solid-phase radioimmunoassay to measure soluble beta 2-M, and an ELISA to measure membrane beta 2-M. Using these methods we found that the levels of beta 2-M in the cell membrane or on the cell surface did not change during monocyte activation. However, activation did induce a significant increase in the concentration of beta 2-M in monocyte supernatants, indicating that beta 2-M synthesis by monocytes is increased during monocyte activation. These results suggest that monocyte activation by hemodialysis membranes may be a contributing factor to the observed increase in circulating beta 2-M levels.