title: Beta-2-microglobulin synthesis is increased during activation of human monocytes.
abstract: 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.
authors.affiliation: Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, N.Y.
authors.forename: P J
authors.initials: PJ
authors.lastname: Knudsen
authors.forename: A K
authors.initials: AK
authors.lastname: Ng
authors.forename: Z R
authors.initials: ZR
authors.lastname: Liu
mesh_terms: D001427:Bacterial Toxins; D004768:Enterotoxins / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D006435:Renal Dialysis; D018089:Superantigens; D014407:Tumor Cells, Cultured / Q000032:analysis / Q000187:drug effects; D001613:beta 2-Microglobulin / Q000096:biosynthesis*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D018089:Superantigens; D001613:beta 2-Microglobulin; C030107:enterotoxin F, Staphylococcal