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Research Article Free access | 10.1172/JCI106871

Complete Deficiency of Leukocyte Glucose-6-Phosphate Dehydrogenase with Defective Bactericidal Activity

M. Robert Cooper, Lawrence R. DeChatelet, Charles E. McCall, Mariano F. La Via, Charles L. Spurr, and Robert L. Baehner

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 Cooper, 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 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

Published in Volume 51, Issue 4 on April 1, 1972
J Clin Invest. 1972;51(4):769–778. https://doi.org/10.1172/JCI106871.
© 1972 The American Society for Clinical Investigation
Published April 1, 1972 - Version history
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Abstract

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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