Up‐regulation of NADPH oxidase components and increased production of interferon‐gamma by leukocytes from sickle cell disease patients

• Published in: American journal of hematology Vol. 83; no. 1; pp. 41 - 45
• Main Authors: Marçal, Lívia E., Dias‐da‐Motta, Péricles M., Rehder, Jussara, Mamoni, Ronei L., Blotta, Maria Heloísa S.L., Whitney, Constance B., Newburger, Peter E., Costa, Fernando F., Saad, Sara T.O., Condino‐Neto, Antonio
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2008; Wiley-Liss
• Subjects: Adolescent; Adult; Anemia, Sickle Cell - metabolism; Anemias. Hemoglobinopathies; Biological and medical sciences; Diseases of red blood cells; Female; Gene Expression Regulation, Enzymologic; Hematologic and hematopoietic diseases; Humans; Interferon-gamma - biosynthesis; Isoenzymes - genetics; Isoenzymes - metabolism; Leukocytes - metabolism; Male; Medical sciences; Middle Aged; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; Phosphorylation; RNA, Messenger - genetics; Transcription, Genetic - genetics; Tumor Necrosis Factor-alpha - biosynthesis; Up-Regulation; Human; Hemoglobinopathy; Immunopathology; Hemolytic anemia; Sickle cell anemia; Hematology; Hemopathy; Biosynthesis; Leukocyte disease; NAD(P)H oxidase; Genetic disease; Gamma interferon
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.20991

We have previously demonstrated that mononuclear leukocytes from patients with sickle cell disease (SCD) release higher amounts of superoxide compared with normal controls. The aim of this study was to further study the NADPH oxidase system in these patients by investigating gene expression of NADPH oxidase components, phosphorylation of p47phox component, and the release of cytokines related to NADPH oxidase activation in mononuclear leukocytes from patients with SCD. gp91phox gene expression was significantly higher in monocytes from SCD patients compared with normal controls (P = 0.036). Monocytes from SCD patients showed higher levels of p47phox phosphorylation compared with normal controls. INF‐γ release by lymphocytes from SCD patients was significantly higher compared with normal controls, after 48 h culture with phytohemagglutinin (P = 0.02). The release of TNF‐α by monocytes from SCD patients and normal controls was similar after 24 and 48 h culture with lipopolysaccharide (P > 0.05). We conclude that monocytes from SCD patients show higher levels of gp91phox gene expression and p47phox phosphorylation, along with increased IFN‐γ release by SCD lymphocytes. These findings help to explain our previous observation showing the increased respiratory burst activity of mononuclear leukocytes from SCD patients and may contribute to inflammation and tissue damage in these patients. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.