PMID- 15044196
OWN - NLM
STAT- MEDLINE
DCOM- 20040903
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 287
IP  - 2
DP  - 2004 Aug
TI  - Role of adhesion and contraction in Rac 1-regulated endothelial barrier function 
      in vivo and in vitro.
PG  - H704-11
AB  - We demonstrated previously that inhibition of the small GTPase Rac-1 by 
      Clostridium sordellii lethal toxin (LT) increased the hydraulic conductivity 
      (L(p)) of rat venular microvessels and induced gap formation in cultured 
      myocardial endothelial cells (MyEnd). In MyEnd cells, we also demonstrated that 
      both LT and cytochalasin D reduced cellular adhesion of vascular endothelial 
      (VE)-cadherin-coated beads. Here we further evaluate the contribution of actin 
      depolymerization, myosin-based contraction, and VE-cadherin linkage to the actin 
      cytoskeleton to LT-induced permeability. The actin-depolymerizing agent 
      cytochalasin D increased L(p) in single rat mesenteric microvessels to the same 
      extent as LT over 80 min. However, whereas the actin-stabilizing agent 
      jasplakinolide blunted the L(p) increase due to cytochalasin D by 78%, it had no 
      effect on the LT response. This conforms to the hypothesis that the predominant 
      mechanism whereby Rac-1 stabilizes the endothelial barrier in intact microvessels 
      is separate from actin polymerization and likely at the level of the VE-cadherin 
      linkage to the actin cytoskeleton. In intact vessels, neither inhibition of 
      contraction (butanedione monoxime, an inhibitor of myosin ATPase) nor inhibition 
      of Rho kinase (Y-27632) modified the response to LT, even though both inhibitors 
      lowered resting L(p). In contrast butanedione monoxime and inhibition of myosin 
      light chain kinase completely inhibited LT-induced intercellular gap formation 
      and largely reduced the LT-induced permeability increase in MyEnd monolayers. 
      These results support the hypothesis that the contractile mechanisms that 
      contribute to the formation of large gaps between cultured endothelial cells 
      exposed to inflammatory conditions do not significantly contribute to increased 
      permeability in intact microvessels.
FAU - Waschke, J
AU  - Waschke J
AD  - Institute of Anatomy and Cell Biology, University of Wurzburg, Wurzburg, Germany.
FAU - Drenckhahn, D
AU  - Drenckhahn D
FAU - Adamson, R H
AU  - Adamson RH
FAU - Curry, F E
AU  - Curry FE
LA  - eng
GR  - HL-28607/HL/NHLBI NIH HHS/United States
GR  - HL-44485/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040325
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Actins)
RN  - 0 (Amides)
RN  - 0 (Antigens, CD)
RN  - 0 (Azepines)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Cadherins)
RN  - 0 (Depsipeptides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Naphthalenes)
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Pyridines)
RN  - 0 (cadherin 5)
RN  - 0 (lethal toxin LT, Clostridium sordellii)
RN  - 102396-24-7 (jasplakinolide)
RN  - 109376-83-2 (ML 7)
RN  - 138381-45-0 (Y 27632)
RN  - 19SQ93LM6H (diacetylmonoxime)
RN  - 22144-77-0 (Cytochalasin D)
RN  - EC 3.6.4.1 (Myosins)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - K324J5K4HM (Diacetyl)
SB  - IM
MH  - Actins/metabolism
MH  - Amides/pharmacology
MH  - Animals
MH  - Antigens, CD
MH  - Azepines/pharmacology
MH  - Bacterial Toxins/pharmacology
MH  - Cadherins/physiology
MH  - Capillary Permeability/drug effects/*physiology
MH  - Cell Adhesion/physiology
MH  - Cell Line, Transformed
MH  - Cytochalasin D/pharmacology
MH  - Cytoskeleton/drug effects
MH  - *Depsipeptides
MH  - Diacetyl/*analogs & derivatives/pharmacology
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Extracellular Space/drug effects
MH  - Mice
MH  - Microcirculation/physiology
MH  - Myosins/physiology
MH  - Naphthalenes/pharmacology
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
MH  - Peptides, Cyclic/pharmacology
MH  - Pyridines/pharmacology
MH  - Rats
MH  - Splanchnic Circulation/*physiology
MH  - Vasoconstriction/*physiology
MH  - rac1 GTP-Binding Protein/*physiology
EDAT- 2004/03/27 05:00
MHDA- 2004/09/04 05:00
CRDT- 2004/03/27 05:00
PHST- 2004/03/27 05:00 [pubmed]
PHST- 2004/09/04 05:00 [medline]
PHST- 2004/03/27 05:00 [entrez]
AID - 01076.2003 [pii]
AID - 10.1152/ajpheart.01076.2003 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2004 Aug;287(2):H704-11. doi: 
      10.1152/ajpheart.01076.2003. Epub 2004 Mar 25.