PMID- 1541673
OWN - NLM
STAT- MEDLINE
DCOM- 19920407
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 89
IP  - 3
DP  - 1992 Mar
TI  - Tumor necrosis factor-alpha-mediated decrease in glutathione increases the 
      sensitivity of pulmonary vascular endothelial cells to H2O2.
PG  - 794-802
AB  - We examined the effects of tumor necrosis factor-alpha (TNF alpha) stimulation of 
      endothelial cells on the increase in endothelial permeability induced by H2O2. 
      Bovine pulmonary microvascular endothelial cells (BPMVEC) were grown to 
      confluence on a microporous filter and the 125I-albumin clearance rate across the 
      monolayer was determined. Pretreatment with TNF alpha (100 U/ml) for 6 h had no 
      direct effect on transendothelial 125I-albumin permeability. However, TNF alpha 
      pretreatment enhanced the susceptibility of BPMVEC to H2O2; that is, H2O2 (10 
      microM) alone had no direct effect, whereas H2O2 increased 125I-albumin 
      permeability more than threefold when added to monolayers pretreated for 6 h with 
      TNF alpha. Determination of lactate dehydrogenase release indicated that 
      increased permeability was not due to cytolysis. We measured the intracellular 
      contents of GSH and catalase to determine their possible role in mediating the 
      increased susceptibility to H2O2. TNF alpha treatment (100 U/ml for 6 h) 
      decreased total GSH content and concomitantly increased the oxidized GSH content, 
      but did not alter the cellular catalase activity. The role of GSH was examined by 
      pretreating endothelial cells with 2 mM GSH for 3 h, which produced an 80% 
      increase in intracellular GSH content. GSH repletion inhibited the increased 
      sensitivity of the TNF alpha-treated endothelial cells to H2O2. We tested the 
      effects of xanthine oxidase (XO) inhibition since XO activation may be a source 
      of oxidants responsible for the decrease in cellular GSH content. Pretreatment 
      with 0.5 mM oxypurinol attenuated the synergistic effect of TNF alpha and H2O2 on 
      endothelial permeability. The results indicate that decreased oxidant buffering 
      capacity secondary to TNF alpha-induced reduction in intracellular GSH content 
      mediates the increased susceptibility of endothelial cells to H2O2. This 
      mechanism may contribute to oxidant-dependent vascular endothelial injury in 
      septicemia associated with TNF alpha release.
FAU - Ishii, Y
AU  - Ishii Y
AD  - Department of Physiology and Cell Biology, Albany Medical College of Union 
      University, New York 12208.
FAU - Partridge, C A
AU  - Partridge CA
FAU - Del Vecchio, P J
AU  - Del Vecchio PJ
FAU - Malik, A B
AU  - Malik AB
LA  - eng
GR  - HL-27106/HL/NHLBI NIH HHS/United States
GR  - HL-32418/HL/NHLBI NIH HHS/United States
GR  - HL-45638/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.6 (Catalase)
RN  - G97OZE5068 (Oxypurinol)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Capillary Permeability/*drug effects
MH  - Catalase/analysis
MH  - Cattle
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*drug effects
MH  - Glutathione/*analysis/pharmacology
MH  - Hydrogen Peroxide/*toxicity
MH  - Lung/blood supply/drug effects
MH  - Oxypurinol/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC442924
EDAT- 1992/03/01 00:00
MHDA- 1992/03/01 00:01
PMCR- 1992/03/01
CRDT- 1992/03/01 00:00
PHST- 1992/03/01 00:00 [pubmed]
PHST- 1992/03/01 00:01 [medline]
PHST- 1992/03/01 00:00 [entrez]
PHST- 1992/03/01 00:00 [pmc-release]
AID - 10.1172/JCI115658 [doi]
PST - ppublish
SO  - J Clin Invest. 1992 Mar;89(3):794-802. doi: 10.1172/JCI115658.