Hemodialysis-Related Induction of β2-Microglobulin Synthesis and Release by Mononuclear Phagocytes

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Abstract
We have investigated β2-microglobulin (β2M) synthesis and release by blood leukocytes and isolated mononuclear phagocytes. Since β2M was discovered to form amyloid fibrils in patients undergoing long term, chronic hemodialysis and monomeric β2M levels in plasma of these patients are highly elevated, and since hemodialysis-related factors that increase β2M production are unknown, we evaluated β2M production by mononuclear phagocytes under a variety of conditions. We utilized a novel enzyme-lined immunoabsorbant assay to quantitate β2M release. Adherence of macrophages onto polystyrene or Cuprophan membranes does not induce β2M synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin 1 induces synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin 1 induces synthesis and release of β2M, indicating that β2M synthesis is increased during macrophage activation. Exposing leukocytes or macrophages to changes in osmotic or oncotic pressure induces a rapid release of β2M and interleukin 1 into the cellular medium. These results suggest that during hemodialysis, β2M production is more likely to result from endotoxin contamination, or osmotic and oncotic changes, rather than direct interaction of mononuclear phagocytes with cellulosic membranes.