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Research Article Free access | 10.1172/JCI106871
Department of Biochemistry, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Department of Medicine, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Division of Research Hematology, Department of Medicine, Children's Hospital Medical Center, Harvard Medical School, Boston, Massachusetts 02100
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Department of Biochemistry, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Department of Medicine, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Division of Research Hematology, Department of Medicine, Children's Hospital Medical Center, Harvard Medical School, Boston, Massachusetts 02100
Find articles by DeChatelet, L. in: JCI | PubMed | Google Scholar
Department of Biochemistry, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Department of Medicine, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Division of Research Hematology, Department of Medicine, Children's Hospital Medical Center, Harvard Medical School, Boston, Massachusetts 02100
Find articles by McCall, C. in: JCI | PubMed | Google Scholar
Department of Biochemistry, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Department of Medicine, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Division of Research Hematology, Department of Medicine, Children's Hospital Medical Center, Harvard Medical School, Boston, Massachusetts 02100
Find articles by La Via, M. in: JCI | PubMed | Google Scholar
Department of Biochemistry, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Department of Medicine, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Division of Research Hematology, Department of Medicine, Children's Hospital Medical Center, Harvard Medical School, Boston, Massachusetts 02100
Find articles by Spurr, C. in: JCI | PubMed | Google Scholar
Department of Biochemistry, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Department of Medicine, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103
Division of Research Hematology, Department of Medicine, Children's Hospital Medical Center, Harvard Medical School, Boston, Massachusetts 02100
Find articles by Baehner, R. in: JCI | PubMed | Google Scholar
Published April 1, 1972 - More info
A 52 yr old Caucasian female (F. E.) had hemolytic anemia, a leukemoid reaction, and fatal sepsis due to Escherichia coli. Her leukocytes ingested bacteria normally but did not kill catalase positive Staphylococcus aureus, Escherichia coli, and Serratia marcescens. An H2O2-producing bacterium, Streptococcus faecalis, was killed normally. Granule myeloperoxidase, acid and alkaline phosphatase, and beta glucuronidase activities were normal, and these enzymes shifted normally to the phagocyte vacuole (light and electron microscopy). Intravacuolar reduction of nitroblue tetrazolium did not occur. Moreover, only minimal quantities of H2O2 were generated, and the hexose monophosphate shunt (HMPS) was not stimulated during phagocytosis.
These observations suggested the diagnosis of chronic granulomatous disease. However, in contrast to control and chronic granulomatous disease leukocytes, glucose-6-phosphate dehydrogenase activity was completely absent in F. E. leukocytes whereas NADH oxidase and NADPH oxidase activities were both normal. Unlike chronic granulomatous disease, methylene blue did not stimulate the hexose monophosphate shunt in F. E. cells. Thus, F. E. and chronic granulomatous disease leukocytes appear to share certain metabolic and bactericidal defects, but the metabolic basis of the abnormality differs. Chronic granulomatous disease cells lack oxidase activity which produces H2O2; F. E. cells had normal levels of oxidase activity but failed to produce NADPH due to complete glucose-6-phosphate dehydrogenase deficiency. These data indicate that a complete absence of leukocyte glucose-6-phosphate dehydrogenase with defective hexose monophosphate shunt activity is associated with low H2O2 production and inadequate bactericidal activity, and further suggest an important role for NADPH in the production of H2O2 in human granulocytes.
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