全身性紅斑狼瘡病人多形核嗜中性白血球葡萄糖傳送蛋白的表現及其功能的研究
Date Issued
2004
Date
2004
Author(s)
謝松洲
DOI
922314B002146
Abstract
Systemic lupus erythematosus (SLE) is characterized with production of
variable autoantibodies and associated immune dysfunction. Patients with SLE are
also susceptible to infections, which are partly due to functional impairment of
polymorphonuclear neutrophils (PMN). Multiple dysfunction of SLE PMN, including
phagocytosis, cytokine production and membrane protein expression etc., was found,
but the real pathogenesis is still unclear. Glucose, the primary substrate of energy
supply, plays a crucial role in survival and functional maintenance in leukocytes. We
determined the membrane expression of glucose transporter (GLUT) by flow
cytometry and measured the glucose uptake by use of non-metabolizable glucose
analog (NBDG) detected by flow cytometry. The lactate production via anaerobic
glycolysis due to ineffective energy supplement in culture supernatant was also
measured by ELISA method. The results revealed defective membrane expression of
GLUT3 and GLUT6 but not GLUT1 in SLE PMN compared to control PMN, and
more significant down-regulation of GLUT expression by LPS or TNF-α stimulation
in SLE PMN. Moreover, the glucose uptake was decreased in SLE PMN during 24h
culture and poor response to LPS-stimulated glucose uptake as in normal PMN. The
increased lactate production reflected the ineffective or insufficiency of glucose
supply indirectly in SLE PMN. According to the above findings, defective membrane
expression of GLUT and associated impaired glucose uptake resulted in functional
impairment in SLE PMN, especially under the stimulation of cytokine or bacterial
product LPS. Bioenergetics might play a critical role in the pathogenesis of PMN
dysfunction in SLE. But the real mechanism of defective energy supply and the
association with underlying autoimmunity need to be further studied.
Subjects
polymorphonuclear neutrophil
glucose transporter
bioenergetics
systemic lupus erythematosus
Publisher
臺北市:國立臺灣大學醫學院內科
Type
report
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