PMID- 8476021
OWN - NLM
STAT- MEDLINE
DCOM- 19930517
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 264
IP  - 4 Pt 1
DP  - 1993 Apr
TI  - TNF-alpha induces endothelial cell F-actin depolymerization, new actin synthesis, 
      and barrier dysfunction.
PG  - C894-905
AB  - Tumor necrosis factor-alpha (TNF-alpha) influences pulmonary vascular endothelial 
      barrier function in vitro. We studied whether recombinant TNF-alpha (rTNF-alpha) 
      regulates endothelial barrier function through actin reorganization. 
      Postconfluent bovine pulmonary artery endothelial cell monolayers were exposed to 
      human rTNF-alpha (1,000 U/ml) and evaluated for 1) transendothelial [14C]albumin 
      flux, 2) F-actin organization with fluorescence microscopy, 3) F-actin 
      quantitation by spectrofluorometry, and 4) monomeric G-actin levels by the 
      deoxyribonuclease I inhibition assay. rTNF-alpha induced increments in 
      [14C]albumin flux (P < 0.04) and intercellular gap formation at > or = 2-6 h. 
      During this same time, the endothelial F-actin pool decreased (P = 0.0064), with 
      reciprocal increases in the G-actin pool (P < 0.0001). Prior F-actin 
      stabilization with phallicidin protected against the rTNF-alpha-induced 
      increments in G-actin (P < 0.002) as well as changes in barrier function (P < 
      0.01). Prior protein synthesis inhibition enhanced the rTNF-alpha-induced 
      decrement in F-actin (P < 0.0001), blunted the G-actin increment (P < 0.002), and 
      increased rTNF-alpha-induced changes in endothelial barrier function (P < 0.003). 
      Therefore, rTNF-alpha induces pulmonary vascular endothelial F-actin 
      depolymerization, intercellular gap formation, and barrier dysfunction. 
      rTNF-alpha also increased total actin (P < 0.02) and new actin synthesis (P < 
      0.002), which may be a compensatory endothelial cell response to 
      rTNF-alpha-induced F-actin depolymerization.
FAU - Goldblum, S E
AU  - Goldblum SE
AD  - Department of Medicine, Department of Veterans Affairs Medical Center, Baltimore, 
      Maryland.
FAU - Ding, X
AU  - Ding X
FAU - Campbell-Washington, J
AU  - Campbell-Washington J
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Actins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3CHI920QS7 (Cytochalasin B)
RN  - 98600C0908 (Cycloheximide)
SB  - IM
MH  - Actins/chemistry/drug effects/*metabolism
MH  - Animals
MH  - Cattle
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cycloheximide/pharmacology
MH  - Cytochalasin B/pharmacology
MH  - Endothelium, Vascular/cytology/drug effects/*metabolism
MH  - Immunoblotting
MH  - Kinetics
MH  - Microscopy, Fluorescence
MH  - Pulmonary Artery
MH  - Recombinant Proteins/pharmacology
MH  - Spectrometry, Fluorescence
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1993/04/01 00:00
MHDA- 1993/04/01 00:01
CRDT- 1993/04/01 00:00
PHST- 1993/04/01 00:00 [pubmed]
PHST- 1993/04/01 00:01 [medline]
PHST- 1993/04/01 00:00 [entrez]
AID - 10.1152/ajpcell.1993.264.4.C894 [doi]
PST - ppublish
SO  - Am J Physiol. 1993 Apr;264(4 Pt 1):C894-905. doi: 
      10.1152/ajpcell.1993.264.4.C894.