Study on the Telomere Length and Its Affecting Factors of Peripheral Blood Mononuclear Cells and Polymorphonuclear Cells in Patients with Systemic Lupus Erythematosus
Date Issued
2004
Date
2004
Author(s)
DOI
zh-TW
Abstract
Systemic lupus erythematosus (SLE) is characterized with aberrant immune regulation and defective function of various leukocytes. CD4+ T cell is the central role of the pathogenesis of SLE, and excessive production of high-affinity pathogenic autoantibodies is T cell driven. The chronic activation/proliferation could lead to premature immune senescence, such as exit from mitotic cycle, low responsiveness to new antigen stimuli and/or cell death. One of the SLE lymphocytes abnormalities is premature immunosenescence and may be associated with the shortening of telomere. Due to the end-replication problem of the linear chromosome during cell division, the telomere length of eukaryotic cell shortens at a rate of 50-200 base pairs per year if no compensatory mechanism, for example, telomerase exists. When telomere shortens to a critical size (<=5kb in mammalian cells), it signals the exit from the mitotic cycle and the onset of cellular senescence. The minimum size of telomere length has an important role in the chromosome integrity and the viability of cell. Telomere length can be an indicator of the cell’s replicative history and their residual replicative potential. Cellular aging has been proved related to the accelerated shortening of the telomere. In autoimmune condition of rheumatoid arthritis, CD4+ T cell presented with features of premature immunosenescence and accelerated telomere shortening. Polymorphonuclear cells (PMN) are terminally differentiated cell without expression of telomerase activity and do not undergo cell division. However, the PMN also have attrition of telomere length. Our study showed accelerated telomere shortening was noted not only in peripheral blood mononuclear cells (MNC), but also in PMN. SLE per se and disease activity had marked effect on the rapid loss of telomere length of these cells. There was a high positive correlation of the telomere length of MNC with that of PMN in normal controls as well as in SLE patients, but the telomere length between these cells in the same subjects was not significant. However, in SLE patients with leucopenia, the telomere length of MNC was significantly shorter than that of PMN. Persistent activation and proliferation of MNC, increased apoptosis or accelerated destruction of MNC as well as PMN, and elevated oxidative stress might contribute to the rapid loss of telomere length in these cells. Telomere shortening of lymphocytes had been linked to the immunosenescence of the immune system. From our study, it might be to say MNC and PMN in SLE patients had premature aging for 16.5 year and 13.4 year, respectively. In the future, we plan to study the effect of various autoantibodies, cytokines, or antioxidants on the function, telomere length, telomerase activity, and immunosenescence markers of MNC and PMN in patients with SLE and try to delay or treat the premature immunosenescence in these patients.
Subjects
週邊血液單核細胞
嗜中性白血球
終端體
紅斑性狼瘡
telomere length
polymorphonuclear cells
SLE
lupus
peripheral blood mononuclear cells
Type
text