PMID- 11792637
OWN - NLM
STAT- MEDLINE
DCOM- 20020307
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 282
IP  - 2
DP  - 2002 Feb
TI  - TNF-alpha disruption of lung endothelial integrity: reduced integrin mediated 
      adhesion to fibronectin.
PG  - L316-29
AB  - Tumor necrosis factor-alpha (TNF-alpha) causes an increase in transendothelial 
      protein permeability of confluent monolayers of calf pulmonary artery endothelial 
      (CPAE) cells, and the addition of plasma fibronectin (pFn) to the culture medium 
      can attenuate this increase in permeability. We determined if reduced integrin 
      function had a role in decreased endothelial cell adhesion to immobilized Fn 
      after exposure of the endothelial monolayers to TNF-alpha. TNF-alpha also causes 
      a reorganization of the subendothelial Fn rich matrix and a significant loss in 
      RGD-dependent adhesion of TNF-alpha treated CPAE cells to pFn coated surfaces. 
      However, flow cytometry revealed no decrease in alpha(5)beta(1) or total beta(1) 
      integrin expression on the surface of the CPAE cells after TNF-alpha. Reduced 
      CPAE adhesion to immobilized Fn was, in part, due to a loss of beta(1)-integrin 
      function since the beta(1)-integrin blocking antibody mAb 13 significantly (P < 
      0.05) prevented the adhesion of normal control CPAE cells but did not further 
      reduce the adhesion of TNF-alpha-treated cells. In addition, antibodies which 
      activate beta(1) integrins restored (P < 0.05) adhesion of TNF-alpha-treated 
      cells to immobilized pFn but did not alter the adhesion of control cells. Despite 
      reduced ability to adhere to immobilized Fn, TNF-alpha-treated CPAE monolayers 
      demonstrated increased binding and incorporation of fluid-phase pFn into the 
      subendothelial extracellular matrix (ECM) as measured by the analysis of the 
      deoxycholate (DOC) detergent insoluble pool of (125)I-Fn in the cell layer. In 
      contrast to the RGD-mediated adhesion of CPAE cells to matrix Fn, the increased 
      binding of soluble pFn after TNF-alpha was not inhibited by RGD peptides or mAb 
      13. Thus reduced integrin-dependent adhesion of the CPAE cells to matrix Fn as 
      well as disruption of the Fn matrix may contribute to the increased protein 
      permeability of previously confluent endothelial monolayer after TNF-alpha. In 
      addition, increased ability for the monolayer to incorporate fluid-phase Fn into 
      the ECM after TNF-alpha via a non-beta(1)- integrin dependent mechanism may be a 
      compensatory response to stabilize the Fn matrix and the endothelial barrier.
FAU - Rotundo, Robert F
AU  - Rotundo RF
AD  - Department of Physiology and Cell Biology, Neil Hellman Medical Research 
      Building, Albany Medical College, Albany, New York 12208, USA.
FAU - Curtis, Theresa M
AU  - Curtis TM
FAU - Shah, Melissa D
AU  - Shah MD
FAU - Gao, Baochong
AU  - Gao B
FAU - Mastrangelo, Anthony
AU  - Mastrangelo A
FAU - LaFlamme, Susan E
AU  - LaFlamme SE
FAU - Saba, Thomas M
AU  - Saba TM
LA  - eng
GR  - F32-HL-010201/HL/NHLBI NIH HHS/United States
GR  - GM-21447/GM/NIGMS NIH HHS/United States
GR  - GM-51540/GM/NIGMS NIH HHS/United States
GR  - T32 HL-07529/HL/NHLBI NIH HHS/United States
GR  - T32-GM-07033/GM/NIGMS NIH HHS/United States
GR  - T32-HL-07194/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, Surface)
RN  - 0 (Epitopes)
RN  - 0 (Fibronectins)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Fibronectin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 42Z2K6ZL8P (Manganese)
RN  - 78VO7F77PN (arginyl-glycyl-aspartic acid)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antigens, Surface/analysis
MH  - Capillary Permeability/drug effects/physiology
MH  - Cattle
MH  - Cell Adhesion/drug effects/physiology
MH  - Cells, Cultured
MH  - Endothelium, Vascular/chemistry/*cytology/metabolism
MH  - Epitopes/analysis
MH  - Extracellular Matrix/metabolism
MH  - Fibronectins/*metabolism
MH  - Flow Cytometry
MH  - Iodine Radioisotopes
MH  - Manganese/pharmacology
MH  - Microscopy, Interference
MH  - Oligopeptides/metabolism/pharmacology
MH  - Pulmonary Artery/cytology
MH  - Receptors, Fibronectin/analysis/immunology/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
EDAT- 2002/01/17 10:00
MHDA- 2002/03/08 10:01
CRDT- 2002/01/17 10:00
PHST- 2002/01/17 10:00 [pubmed]
PHST- 2002/03/08 10:01 [medline]
PHST- 2002/01/17 10:00 [entrez]
AID - 10.1152/ajplung.00145.2000 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2002 Feb;282(2):L316-29. doi: 
      10.1152/ajplung.00145.2000.