PMID- 11966760
OWN - NLM
STAT- MEDLINE
DCOM- 20020904
LR  - 20190513
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 127
IP  - 3
DP  - 2002 Mar
TI  - Intravenous immunoglobulin (IVIG) preparations induce apoptosis in 
      TNF-alpha-stimulated endothelial cells via a mitochondria-dependent pathway.
PG  - 445-54
AB  - Endothelial cells (ECs) are a target in inflammation, and the death of EC is 
      regulated by various factors. Although intravenous immunoglobulin (IVIG) 
      preparations are known to be beneficial therapeutic agents for the treatment of 
      autoimmune diseases and systemic inflammatory disorders, their mechanism of 
      action have not yet been completely elucidated. The aim of the present study is 
      to investigate the possible role of IVIG in EC apoptosis. We demonstrate herein 
      that IVIG induced the apoptosis of human umbilical vein ECs (HUVECs) 
      prestimulated by TNF-alpha in vitro, but not in unstimulated HUVECs, in a dose- 
      and time-dependent manner, using a proportion of cells with hypodiploid DNA, DNA 
      ladder formation and morphological changes. Anti-Fas MoAbs had no effect on the 
      IVIG-induced apoptosis in the TNF-alpha-stimulated HUVECs. IVIG decreased the 
      intracellular expression of anti-apoptotic proteins of the Bcl-2 family (A1 and 
      Bcl-XL) while IVIG increased the intracellular expression of pro-apoptotic 
      proteins (Bax and Bcl-XS) in the TNF-alpha-stimulated HUVECs. Furthermore, IVIG 
      increased the intracellular production of reactive oxygen species and decreased 
      the mitochondrial membrane potential (Delta(psi)m). Caspase-inhibitors inhibited 
      the IVIG-induced apoptosis of the TNF-alpha-stimulated HUVECs. The present 
      results show a novel action in which IVIG can induce the apoptosis of 
      TNF-alpha-stimulated HUVECs through a mitochondrial apoptotic signalling pathway. 
      These observations suggest that the clinical use of IVIG preparations may thereby 
      regulate the cell death of activated ECs in inflammation.
FAU - Nakatani, K
AU  - Nakatani K
AD  - Department of Paediatrics, National Defense Medical College, Tokorozawa, Saitama, 
      Japan.
FAU - Takeshita, S
AU  - Takeshita S
FAU - Tsujimoto, H
AU  - Tsujimoto H
FAU - Sekine, I
AU  - Sekine I
LA  - eng
PT  - Journal Article
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
SB  - IM
MH  - *Apoptosis
MH  - Caspase Inhibitors
MH  - Cells, Cultured
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Endothelium, Vascular/*cytology/drug effects/metabolism
MH  - Humans
MH  - Immunoglobulin Fab Fragments/pharmacology
MH  - Immunoglobulin Fc Fragments/pharmacology
MH  - Immunoglobulins, Intravenous/*pharmacology
MH  - Kinetics
MH  - Membrane Potentials
MH  - Mitochondria/*physiology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - fas Receptor/physiology
PMC - PMC1906310
EDAT- 2002/04/23 10:00
MHDA- 2002/09/06 10:01
PMCR- 2003/03/01
CRDT- 2002/04/23 10:00
PHST- 2002/04/23 10:00 [pubmed]
PHST- 2002/09/06 10:01 [medline]
PHST- 2002/04/23 10:00 [entrez]
PHST- 2003/03/01 00:00 [pmc-release]
AID - 1769 [pii]
AID - 10.1046/j.1365-2249.2002.01769.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2002 Mar;127(3):445-54. doi: 10.1046/j.1365-2249.2002.01769.x.