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Fibrinogen induces endothelial cell adhesion and spreading via the release
of endogenous matrix proteins and the recruitment of more than one integrin
receptor
E Dejana, MG Lampugnani, M Giorgi, M Gaboli and PC Marchisio
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
We have previously shown that fibrinogen (fg) acts as a subendothelial
matrix protein in promoting human endothelial cell (EC) adhesion and
cytoskeletal organization. In this study we report that EC spreading on fg,
at variance with other matrix proteins, requires endogenous matrix protein
synthesis and secretion. ECs, upon seeding on fg, promptly released and
organized a fibronectin (fn) matrix. Fg was more effective than vitronectin
(vn) in promoting the deposition of this protein. ECs treated with monensin
to block matrix protein secretion still adhered to fg but did not properly
organize their cytoskeleton and adhesion structures. In contrast, monensin
did not affect EC spreading either on vn or on fn. Using antibodies to the
alpha and beta chains of fn (alpha 5 beta 1) and vn (alpha v beta 3)
receptors, it was found that ECs adherent to fg show clustering and
organization in adhesion structures of both type of receptors. A faint
staining of adhesion structures with alpha 2 but not alpha 3 and alpha 6
antibodies was also observed. Antibodies either to vn or fn receptors were
able to disrupt the EC monolayer and to induce EC retraction and
detachment, thus indicating that both receptors are important in
maintaining a sustained EC adhesion to fg. However, when ECs were treated
with monensin only the vn receptor was organized in adhesion structures
while the fn receptor was diffusely distributed. This suggests that
clustering of the fn receptor is mediated by the release of endogenous
matrix proteins induced by the exposure to fg. In conclusion, fg has a
peculiar and complex type of interaction with ECs since it requires
endogenous matrix protein release and the recruitment of more than one
adhesive receptor. This suggests a specific way of response of ECs to each
extracellular matrix component.
Volume 75,
Issue 7,
pp. 1509-1517,
04/01/1990
Copyright © 1990 by The American Society of Hematology
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