Reactivity of synthetic peptide analogs of adhesive proteins in regard to
the interaction of human endothelial cells with extracellular matrix
CS Chen and J Hawiger
Department of Medicine, New England Deaconess Hospital, Boston, MA.
Vascular endothelial cells, providing a nonthrombogenic surface to the
lumenal aspect of blood vessels, are anchored to matrix adhesion molecules
in the subendothelium through their respective receptors belonging to a
superfamily of integrins. We analyzed the reactivity of synthetic peptide
analogs of adhesive proteins toward human umbilical vein endothelial cells
(HUVEC), assaying their detachment from extracellular matrix and attachment
to extracellular matrix components in vitro. Synthetic peptide analogs
Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), Arg-Gly-Asp-Val (RGDV), Arg-Gly-Asp-Ser
(RGDS), and Arg-Gly-Asp-Phe (RGDF), which are analogous to "cell adhesion
sites" of fibronectin, vitronectin, von Willebrand factor, and alpha-chain
of human fibrinogen, respectively, caused significant detachment of HUVEC
from the extracellular matrix in vitro at the concentrations ranging from
0.5 to 1.5 mmol/L. They also interfered with attachment of HUVEC to
surfaces coated with subendothelial extracellular matrix or its components.
The synthetic peptide analog of HHLGGAKQAGDV, which is homologous to the
gamma-chain of human fibrinogen sequence 400-411, did not cause any
measurable effect on the integrity of HUVEC monolayers (detachment and
attachment). "Hybrid" peptides bearing salient features of both sequences,
ie, Ala-Lys-Gln-Arg-Gly-Asp-Phe (AKQRGDF) and Lys- Gln-Arg-Gly-Asp-Phe
(KQRGDF), had an attenuated effect on the detachment of HUVEC from
extracellular matrix. Thus, the integrity of the human endothelial cell
monolayer anchored to the extracellular matrix, as measured in detachment
and attachment assays, is disturbed by peptides containing RGD sequence
whereas the synthetic peptide His-
His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val (HHLGGAKQAGDV) is nonreactive.
Volume 77,
Issue 10,
pp. 2200-2206,
05/15/1991
Copyright © 1991 by The American Society of Hematology
