Am. J. Respir. Crit. Care Med., Volume 164, Number 7, October 2001, 1248-1252

Increased F₂ Isoprostanes in the Acute Chest Syndrome of Sickle Cell Disease as a Marker of Oxidative Stress

ELIZABETH S. KLINGS, BRIAN W. CHRISTMAN, JAMES MCCLUNG, ARTHUR F. STUCCHI, LILLIAN MCMAHON, MARC BRAUER, and HARRISON W. FARBER

The Pulmonary Center, Department of Surgical Research, Department of Hematology/Oncology, Boston University School of Medicine, Boston, Massachusetts; and Department of Pulmonary/Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee

Nitric oxide metabolism is altered during the acute chest syndrome of sickle cell disease. In the presence of oxygen and oxygen-related molecules, nitric oxide can preferentially form the powerful oxidants nitrite, nitrate, and peroxynitrite. We hypothesized that increased oxidative stress may contribute to the pathogenesis of acute chest syndrome and measured F₂ isoprostanes, a nonenzymatically generated molecule resulting from free radical catalyzed lipid peroxidation in patients with sickle cell disease in various stages of disease. Plasma samples were obtained from nineteen patients with sickle cell disease during acute chest syndrome (pre- and postexchange transfusion), vasoocclusive crisis, and/or at baseline; 12 normal volunteers served as controls. F₂ isoprostanes were measured by gas chromatography/mass spectrophotometry. There was a 9-fold increase in F₂ isoprostanes in patients with acute chest syndrome as compared with normal volunteers. There was approximately a 50-60% decline in isoprostanes postexchange transfusion to a level similar to that of patients with sickle cell disease at baseline. There was no difference in isoprostanes between vasoocclusive crisis and patients with sickle cell disease at baseline. Increased oxidative stress, measured by generation of F₂ isoprostanes, occurs during acute chest syndrome and may have an important role in the pathogenesis of this disease process.

This article has been cited by other articles:

				C. R. Morris, J. H. Suh, W. Hagar, S. Larkin, D. A. Bland, M. H. Steinberg, E. P. Vichinsky, M. Shigenaga, B. Ames, F. A. Kuypers, et al. Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease Blood, January 1, 2008; 111(1): 402 - 410. [Abstract] [Full Text] [PDF]

				M. L. Jison, P. J. Munson, J. J. Barb, A. F. Suffredini, S. Talwar, C. Logun, N. Raghavachari, J. H. Beigel, J. H. Shelhamer, R. L. Danner, et al. Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease Blood, July 1, 2004; 104(1): 270 - 280. [Abstract] [Full Text] [PDF]

				C. R. Morris, S. M. Morris Jr., W. Hagar, J. van Warmerdam, S. Claster, D. Kepka-Lenhart, L. Machado, F. A. Kuypers, and E. P. Vichinsky Arginine Therapy: A New Treatment for Pulmonary Hypertension in Sickle Cell Disease? Am. J. Respir. Crit. Care Med., July 1, 2003; 168(1): 63 - 69. [Abstract] [Full Text] [PDF]

				A K Siddiqui and S Ahmed Pulmonary manifestations of sickle cell disease Postgrad. Med. J., July 1, 2003; 79(933): 384 - 390. [Abstract] [Full Text] [PDF]

				S. H. Salzman Does Splinting From Thoracic Bone Ischemia and Infarction Contribute to the Acute Chest Syndrome in Sickle Cell Disease? Chest, July 1, 2002; 122(1): 6 - 9. [Full Text] [PDF]

				M. J. TOBIN Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2001 Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 642 - 662. [Full Text] [PDF]