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 beta-galactosidase of inflammation-primed B lymphocytes and sialidase of T lymphocytes. The treatment of human peripheral blood mononuclear cells with an inflammatory lysophospholipid induced beta-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 beta-galactosidase activity of B lymphocytes as well as that of the sialidase of T lymphocytes was found to be defective in these patients.
Yamamoto
N
N
Laboratory of Cancer Immunology and Molecular Biology, Albert Einstein Cancer Center, Philadelphia, PA 19141, USA.
Naraparaju
V R
VR
Orchard
P J
PJ
D016026:Bone Marrow Transplantation; D006026:Glycoside Hydrolases / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000201:enzymology; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D009439:Neuraminidase / Q000172:deficiency; D010022:Osteopetrosis / Q000201:enzymology* / Q000628:therapy; D014809:Vitamin D-Binding Protein / Q000378:metabolism*; D001616:beta-Galactosidase / Q000172:deficiency
D016215:Macrophage-Activating Factors; D014809:Vitamin D-Binding Protein; D006026:Glycoside Hydrolases; D009439:Neuraminidase; D001616:beta-Galactosidase