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Analysis of the thiol status of peripheral blood leukocytes in rheumatoid arthritis patients

University of Massachusetts Amherst, Amherst Center, Massachusetts, United States
Journal of Leukocyte Biology (Impact Factor: 4.3). 05/2007; 81(4):934-41. DOI: 10.1189/jlb.0806533
Source: PubMed

ABSTRACT Although the exact etiology of rheumatoid arthritis (RA) remains unknown, there is increasing evidence that reactive oxygen species and a pro-oxidant/antioxidant imbalance are an important part of the pathogenesis of joint tissue injury. Flow cytometry was used to evaluate the thiol status [surface-thiols and intracellular glutathione (iGSH)] of leukocytes from RA patients and controls. Levels of surface-thiols and iGSH of leukocytes from RA patients were significantly lower than of leukocytes from controls. CD53, a glycoprotein of the tetraspanin superfamily, which coprecipitates with the GSH recycling enzyme gamma-glutamyl transpeptidase, was elevated significantly on leukocytes from RA patients compared with leukocytes from controls. Surface-thiols and GSH play important roles in redox buffering of cells, providing protection from oxidative stress. The chronic inflammation of RA has been associated with oxidative stress, which is shown to cause a decline in the levels of cellular antioxidant sulfhydryls (R-SH). As antioxidant-protective levels also decline with age, the problem is compounded in older RA patients, who did have fewer R-SH. Chronic stress can also have an effect on telomere lengths, determining cell senescence and longevity. Although telomeres shorten with increasing age, our flow cytometry studies indicate that accelerated shortening in telomere lengths occurs with increasing age of RA patients, suggesting premature cellular aging. The paradox is that lymphocytes from RA patients are believed to resist apoptosis, and we suggest that the elevated expression of CD53, which results from the increased oxidative stress, may protect against apoptosis.

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    • "The antioxidant glutathione must be recaptured by γ-glutamyl-transpeptidase (GGT) [18]. Because CD53, a glycoprotein of the tetraspanin superfamily, can coprecipitate with GGT activity, elevated CD53 expression in an enhanced oxidative stress environment may prevent cell apoptosis due to oxidative damage [19]. In the present study, we hypothesized that deranged bioenergetics and defective redox capacity, especially in the immune-active cells, may be involved in the molecular basis of cellular immune dysfunction and increased oxidative stress in patients with active SLE. "
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    • "It could be argued that the limited immunoreactivity found in astrocytes for the GS-NEM antibody may be related to the limited ability of NEM to penetrate astrocytic membranes rather than neuronal membranes. However we have previously used this antibody in flow-cytometric experiments to determine GSH activity in leukocytes, in addition to T-cells and B-cells in culture, which suggests that the antibody readily penetrates a variety of cell membranes (Ault and Lawrence, 2003; Pedersen-Lane et al., 2007). The GS-NEM antibody is also sensitive to concentration dependent changes in GSH levels. "
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    • "CD53 is a glycoprotein of the tetraspanin superfamily associated with the recycling enzyme gamma-glutamyl transpeptidase [3]. As such, CD53 plays a role in redox buffering of cells to provide protection from oxidative stress [33] [39]. CD53 expression is elevated in situations of increased oxidative stress such as in rheumatoid arthiritis, radiation damage and also aging, and its expression appears to counter the acceleration of programmed cell death by oxidative damage. "
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