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Thioredoxin and Protein Nitrotyrosine in Bone Marrow Supernatant From Patients With Human Immunodeficiency Virus Infection
  1. An Van Laer,
  2. Gail Dallalio,
  3. Stacey W. McKenzie,
  4. Robert T. Means Jr
  1. From the Division of Hematology/Oncology (A.L., G.D., R.T.M.) Ralph H. Johnson VA Medical Center and the Medical University of South Carolina, Charleston
  2. Division of Infectious Diseases (S.W.M.), Ralph H. Johnson VA Medical Center and the Medical University of South Carolina, Charleston.
  1. Address correspondence to: Robert T. Means, Jr, MD, Hematology/Oncology Division, Medical University of South Carolina, 903 CSB, 96 Jonathan Lucas St, Charleston, SC 29425. E-mail meansr{at}
  2. Supported by funds from the Medical Research Service, Department of Veterans Affairs and by grant HL-53703 from the National Institutes of Health.


Background Balance and imbalance between oxidant stress and antioxidants contributes to the manifestations of human immunodeficiency virus (HIV) infection. Previously, we demonstrated a characteristic cytokine pattern in marrow supernatant from HIV patients who underwent diagnostic examinations.

Methods In this report, we have determined the protein nitrotyrosine (pNT) concentration (an indicator of nitric oxide-superoxide interaction) as well as the concentration of the redox enzyme thioredoxin (Trx) in marrow supernatant from HIV patients, healthy controls, and other patients, and in serum from comparable subjects.

Results pNT concentrations were similar in serum and marrow supernatant and did not differ between subject subsets. Trx concentrations in both marrow supernatant and serum were higher for HIV patients than for other subjects; serum Trx concentrations were significantly higher than marrow Trx concentrations for the non-HIV patients and controls. The ratios of pNT/Trx concentrations in serum were similar in all subsets tested. In marrow aspirate, however, these ratios differed widely and significantly, with the highest values observed in non-HIV patients and the lowest in HIV patients. Only for HIV patients were serum and marrow supernatant pNT/Trx ratios similar. In HIV patients, marrow Trx concentrations correlated with CD4 count, CD4/CD8 ratio, and marrow colony-forming unit E (CFU-E) concentration; marrow pNT concentration correlated with the concentration of tumor necrosis factor in marrow supernatant, and with platelet count. No correlations were observed in other subject subsets.

Conclusions These findings suggest that there is a degree of local regulation of the redox state of the marrow microenvironment that varies with the patients' clinical statuses, and which is associated with effects on hematopoiesis.

Key Words
  • HIV
  • thioredoxin
  • peroxynitrite
  • oxidative stress
  • anemia

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