Defective lymphocyte glycosidases in the macrophage activation cascade of juvenile osteopetrosis

Generation of macrophage-activating factor requires a precursor protein, Gc protein (serum vitamin D₃-binding protein), as well as participation of β-galactosidase of inflammation-primed B lymphocytes and sialidase of T lymphocytes. The treatment of human peripheral blood mononuclear cells with an inflammatory lysophospholipid induced β-galactosidase and sialidase activity of lymphocytes, leading to the generation of macrophage-activating factor and activation of monocytes/macrophages. However, lysophospholipid treatment of peripheral blood mononuclear cells from three infantile patients with osteopetrosis resulted in no significant activation of monocytes/macrophages. The lysophospholipid-inducible β-galactosidase activity of B lymphocytes as well as that of the sialidase of T lymphocytes was found to be defective in these patients.