Endotoxin abolishes the induction of alpha 2-macroglobulin synthesis in cultured human monocytes indicating inhibition of the terminal monocyte maturation into macrophages.

Monocytes were prepared from human blood and allowed to differentiate into macrophages in vitro. Synthesis and secretion of the potent proteinase inhibitor alpha 2-macroglobulin is strongly induced during maturation of monocytes into macrophages establishing alpha 2-macroglobulin as a differentiation marker protein. When the monocytes were incubated with endotoxin (S. typhi) in a concentration as low as 100 ng/ml, induction of alpha 2-macroglobulin synthesis was completely abolished indicating impaired monocyte/macrophage differentiation by lipopolysaccharides (LPS). In contrast to alpha 2-macroglobulin, synthesis of alpha 1-proteinase inhibitor in mononuclear phagocytes was stimulated by endotoxin.