Myeloperoxidase: a myeloid cell nuclear antigen with DNA-binding properties.
An antigen histochemically localized in the nuclei and cytoplasmic granules of normal and leukemic human myeloid cells has been identified as myeloperoxidase (MPO; EC 1.11.1.7). The localization and amount of the enzyme was determined by using a murine monoclonal antibody designated H-43-5 raised against nuclear proteins derived from human promyelocytic HL-60 leukemia cells. The highest amount of nuclear MPO (3.5 micrograms per 10(6) nuclei) was found in granulocytes; less than half of this amount was detected in nuclei from HL-60 cells. Still lower levels were found in nuclei from monocytes and a series of human monomyelocytic leukemia cells. MPO from HL-60 cells was purified by immunoaffinity chromatography and fractionated into three components (forms I, II, and III) by CM-cellulose chromatography. Chromatography of these MPO forms on DNA-Sepharose columns confirmed that all three forms of MPO were tightly bound to DNA with apparent relative affinities in the order of form III greater than form II greater than form I. The affinity of MPO form III for DNA was sufficient to enable the formation and elution of DNA-MPO complexes during size-exclusion chromatography at high ionic strength and neutral pH. This form of MPO was also able to shield DNA from strand scission induced by active oxygen species generated by xanthine oxidase acting aerobically on xanthine. These data suggest that intranuclear MPO may help to protect DNA against damage resulting from oxygen radicals produced during myeloid cell maturation and function.
Murao
S
S
Division of Biological, Environmental, and Medical Research, Argonne National Laboratory, IL 60439-4833.
Stevens
F J
FJ
Ito
A
A
Huberman
E
E
D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D002467:Cell Nucleus / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology*; D007938:Leukemia / Q000201:enzymology / Q000473:pathology; D007962:Leukocytes / Q000201:enzymology; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D009195:Peroxidase / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000201:enzymology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000941:Antigens; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009195:Peroxidase