Natural killer cell-mediated cytotoxicity does not depend on recognition of mannose 6-phosphate residues

• Published in: The Journal of immunology (1950) Vol. 134; no. 1; pp. 65 - 69
• Main Authors: Haubeck, HD, Kolsch, E, Imort, M, Hasilik, A, von Figura, K
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.01.1985; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Cell interactions; Cell Line; Cytotoxicity, Immunologic; Endocytosis; Fibroblasts - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hexosephosphates - analysis; Hexosephosphates - pharmacology; Humans; Hydrolases - analysis; Immune Sera; Immunobiology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Leukemia, Myeloid, Acute; Lysosomes - analysis; Mannosephosphates - analysis; Mucolipidoses - immunology; Natural killer cell; Human; Cell-cell interaction; Enzyme; Cytotoxicity; I cell disease; Cellular immunity; Mannose; Target cell; Mechanism; Biological receptor
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.134.1.65

Interaction of mannose 6-phosphate-specific receptors with their ligands has been suggested to be essential for natural killer cell (NK)-mediated cytotoxicity. Indeed, mannose 6-phosphate-specific receptors and ligands bearing mannose 6-phosphate residues are demonstrable on human peripheral blood leukocytes with NK activity as well as on K-562 NK target cells, allowing at least in principle such an interaction. It can also be shown that NK activity of human peripheral blood leukocytes is inhibited by mannose 6-phosphate. The following observations, however, exclude an essential role of the mannose 6-phosphate receptor-ligand system in NK cell-mediated cytotoxicity. 1) NK cytotoxicity is sensitive to a broad range of structurally unrelated sugar phosphates. 2) NK activity is normal in patients with I cell disease (mucolipidosis II), which due to a genetic defect are unable to synthesize the ligands for the mannose 6-phosphate-specific receptor. 3) NK cytotoxicity is not inhibited by an antiserum against the mannose 6-phosphate receptor, which blocks the receptor function.