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

UMMS Affiliation

Department of Pediatrics

Publication Date


Document Type



Adolescent; Adult; Anemia, Sickle Cell; Female; Gene Expression Regulation, Enzymologic; Humans; Interferon-gamma; Isoenzymes; Leukocytes; Male; Middle Aged; NADPH Oxidase; Phosphorylation; RNA, Messenger; Transcription, Genetic; Tumor Necrosis Factor-alpha; *Up-Regulation


Hematology | Oncology | Pediatrics


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 p47(phox) component, and the release of cytokines related to NADPH oxidase activation in mononuclear leukocytes from patients with SCD. gp91(phox) 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 p47(phox) phosphorylation compared with normal controls. INF-gamma 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-alpha 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 gp91(phox) gene expression and p47(phox) phosphorylation, along with increased IFN-gamma 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.

DOI of Published Version



Am J Hematol. 2008 Jan;83(1):41-5. doi 10.1002/ajh.20991

Journal/Book/Conference Title

American journal of hematology

Related Resources

Link to article in PubMed

PubMed ID