Hemodialysis-Related Induction of β 2 -Microglobulin Synthesis and Release by Mononuclear Phagocytes

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.