Beta-2-Microglobulin Synthesis Is Increased during Activation of Human Monocytes

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Abstract
We have investigated the regulation of β2-microglobulin (β2-M) synthesis by monocytes. Recent interest in β2-M has developed since the discovery that this protein forms amyloid fibrils in patients undergoing long-term, chronic hemodialysis. The β2-M amyloid-osis is linked to the greatly elevated levels of monomeric β2-M in their circulation. Since factors that govern β2-M release from plasma membranes are not known, we endeavored to evaluate β2-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 β2-M. We now present a novel method to purify β2-M, a solid-phase radioimmunoassay to measure soluble β2-M, and an ELISA to measure membrane β2-M. Using these methods we found that the levels of β2-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 β2-M in monocyte supernatants, indicating that β2-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 β2-M levels.

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