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vß3 and 5ß1 Integrins
From the Department of Pathology and Laboratory Medicine, Texas A & M University Health Science Center, College Station, Texas
Recent data have revealed the involvement of the
vß3 integrin in angiogenesis.
However, few studies to date have provided a convincing role
for this receptor in in vitro assays of endothelial cell
morphogenesis where defined steps can be examined. Here, we
present data showing that two integrins,
vß3 and
5ß1, regulate human endothelial
cell vacuolation and lumen formation in three-dimensional fibrin
matrices. Cells resuspended in fibrin formed intracellular vacuoles
that coalesced into lumenal structures. These morphogenic events were
completely inhibited by the simultaneous addition of
anti-vß3 and anti-5
integrin antibodies. Complete blockade was also accomplished with a
combination of the cyclic Arg-Gly-Asp (cRGD) peptide and
anti-5 integrin antibodies. No blockade was observed
with the control Arg-Gly-Glu (RGE) peptide alone or in combination with
control antibodies. Finally, we were able to demonstrate
regression of vacuoles and lumens several hours after the addition of
cRGD peptides combined with anti-5 integrin antibodies.
These effects were not observed with control peptides alone or in
combination with control antibodies. We report here the novel
involvement of both the vß3 and
5ß1 integrins in vacuolation and lumen
formation in a fibrin matrix, implicating a role for multiple
integrins in endothelial cell morphogenesis.
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