Cardiotoxin-III selectively enhances activation-induced apoptosis of human CD8+ T lymphocytes.
Cardiotoxin-III (CTX-III), a major cardiotoxin isolated from the venom of the Taiwan cobra (Naja naja atra), is a highly basic, hydrophobic, toxic protein, which can induce lysis of mononuclear cells by an unknown mechanism. This study was undertaken to investigate the effects of CTX-III on untreated and PHA-activated peripheral blood mononuclear cells (PBMCs) in vitro. The results show that treatment of PHA-activated lymphocytes with CTX-III (10 microg/ml) induced apoptosis and depletion of the CD8(+) population. In both untreated and PHA-treated lymphocytes, interferon-gamma production was dramatically reduced and interleukin-2 (IL-2) production was moderately reduced by CTX-III treatment. In PHA-activated lymphocytes, CD4 expression was increased, whereas CD8 and IL-2R beta chain (CD25) expression were decreased. In contrast, CTX-III had no effect on the viability of PHA-activated monocytes but significantly enhanced their tumor necrosis factor-alpha production. These results show that CTX-III selectively enhanced activation-induced apoptosis in CD8(+) T cells. CTX-III was found to bind to the cell membrane of PHA-stimulated PBMCs, and three CTX-III-binding proteins, with molecular weights of 92, 77, and 68 kDa, were identified. We therefore propose that CTX-III interacts with one or more cell surface proteins and initiates a signal pathway causing functional changes. These findings provide an insight into the immunomodulatory properties of CTX-III and suggest a novel method for the selective induction of apoptosis in CD8(+) T lymphocytes.
Su
Shu-Hui
SH
Department of Cosmetic Science, Chung Hwa College of Medical Technology, Tainan 717 Taiwan.
Su
Shu-Jem
SJ
Lin
Shinne-Ren
SR
Chang
Kee-Lung
KL
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D004179:Cobra Cardiotoxin Proteins / Q000378:metabolism / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004546:Elapid Venoms / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005434:Flow Cytometry; D005562:Formazans / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000378:metabolism; D010835:Phytohemagglutinins / Q000276:immunology / Q000378:metabolism
D004179:Cobra Cardiotoxin Proteins; D016207:Cytokines; D004546:Elapid Venoms; D005562:Formazans; D010835:Phytohemagglutinins; C082202:cardiotoxin III, Naja naja atra; C059088:1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan