全身性紅斑狼瘡患者單核性細胞的異常氧化還原狀態與其免疫反應低下之間關係的研究(1/3)
Date Issued
2005-05-27
Date
2005-05-27
Author(s)
余家利
DOI
932314B002085
Abstract
Objective. Immune hyporesponsiveness of mononuclear cell (MNC) and polymorphonuclear
neutrophils (PMN) predisposes patients with active systemic lupus erythematosus
(SLE) susceptible to infections. This study aimed to explore the pathogenetic factors for it.
Methods. Sixty-three patients in total fulfilling the 1982 revised ACR classification criteria
for SLE and the same number of sex- and age-matched normal individuals were studied.
Reduction-oxidation (redox) capacity [glutathione (GSH) level, GSH peroxidase (GSH-Px)
and GSH reductase (GSSG-R) activities], mitochondrial (mt) functions (mitochondrial
potential, mitochondrial mass, ATP production and mtDNA 4977bp deletion), and
activation-related parameters (membrane potential changes and expression of Na+ and
K+-associated molecules) of MNC and PMN were compared in normal and SLE groups. In
addition, the effects of anti-dsDNA autoantibodies (100IU/ml) purified from active SLE
sera on GSH-Px activity and apoptosis was determined.
Results: The GSH level and GSH-Px activity in SLE-MNC and GSH level in SLE-PMN
are lower than the normal counterparts. The reduced redox capacity in SLE immune cells
seems not relevant to the anti-SLE medications because the same tendency was also
observed in 8 untreated Active SLE patients. The reciprocal expression of GSH-Px isomers
in MNC and PMN was the same in normal and SLE patients in that dimer (50kDa) and
tetramer (100kDa) are prominent in MNC whereas monomer (25kDa) and trimer (75kDa)
are prominent in PMN. The defective redox capacity in SLE immune cells leads to
3
impaired mitochondrial functions with defective ATP production, decreased mitochondrial
mass, reduced mitochondrial potentials, and increased mtDNA 4977bp deletion (18.2% in
SLE vs. 4.3% in normal). The membrane potential of SLE-MNC and PMN was also
diminished due to decreased expression of Na+-K+-ATPase, epithelial Na+ channel and
renal outer medullary K+ channel. Anti-dsDNA antibodies (25-100IU/ml) purified from
SLE sera suppressed GSH-Px activity and increasing normal cells apoptosis.
Conclusion. Reduced redox capacity, and defective Na+ and K+ transport-related molecule
expression are the predisposing factors for immune hyporesponsiveness in patients with
active SLE. Anti-dsDNA autoantibodies play a role on reducing redox capacity in these
patients.
Subjects
systemic lupus erythematosus
immune hyporesponsiveness
redox capacity
mitochondrial function
Na+ and K+ transporters
Publisher
臺北市：國立臺灣大學醫學院分子醫學研究所
Type
journal article
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