Structural modification of serum vitamin D3-binding protein and immunosuppression in AIDS patients.
A serum glycoprotein, vitamin D3-binding protein (Gc protein), can be converted by beta-galactosidase of stimulated B lymphocytes and sialidase of T lymphocytes to a potent macrophage-activating factor (MAF), a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is a precursor for MAF. Treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high-titered MAF (GcMAF). When peripheral blood monocytes/macrophages of 46 HIV-infected patients were treated with GcMAF (100 pg/ml), the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of plasma Gc protein was low in 16 (35%) of of these patients. Loss of the MAF precursor activity appeared to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase found in the patient blood stream. Levels of plasma alpha-N-acetylgalactosaminidase activity in individual patients had an inverse correlation with the MAF precursor activity of their plasma Gc protein. Thus, precursor activity of Gc protein and alpha-N-acetylgalactosaminidase activity in patient blood can serve as diagnostic and prognostic indices.
Yamamoto
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Laboratory of Cancer Immunology and Molecular Biology, Albert Einstein Cancer Center, Philadelphia, Pennsylvania 19141, USA.
Naraparaju
V R
VR
Srinivasula
S M
SM
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000201:enzymology / Q000276:immunology*; D006031:Glycosylation; D006596:Hexosaminidases / Q000097:blood*; D006801:Humans; D007165:Immunosuppression Therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors / Q000097:blood*; D008264:Macrophages / Q000276:immunology; D013379:Substrate Specificity; D014809:Vitamin D-Binding Protein / Q000097:blood* / Q000737:chemistry; D048809:alpha-N-Acetylgalactosaminidase
D016215:Macrophage-Activating Factors; D014809:Vitamin D-Binding Protein; D006596:Hexosaminidases; C482722:NAGA protein, human; D048809:alpha-N-Acetylgalactosaminidase