Cw. Francis et al., ENDOTHELIAL-CELL RESPONSES TO FIBRIN MEDIATED BY FPB CLEAVAGE AND THEAMINO-TERMINUS OF THE BETA-CHAIN, Blood cells, 19(2), 1993, pp. 291-307
Endothelial cells (EC) interact with fibrin at sites of vascular injur
y, thrombosis, inflammation and tumor growth, whereas they are quiesce
nt when exposed to circulating fibrinogen. To determine the structural
basis for specific interaction with fibrin we have characterized the
response of EC to fibrin of varying structure. Fibrin was prepared wit
h thrombin, which cleaves both fibrinopeptide A (FPA) and fibrinopepti
de B (FPB), with Reptilase, which cleaves only FPA, and with contortri
x procoagulant to cleave only FPB. Fibrin with FPB cleavage stimulated
release of von Willebrand factor from EC Weibel-Palade bodies and als
o supported cell spreading. Involvement of the amino terminus of the f
ibrin beta chain in the response was shown by stimulation of von Wille
brand factor release by the peptide beta 15-42. Also, fibrin prepared
from a fibrinogen derivative lacking residues 15-42 of the beta chain
failed to support EC spreading. EC adhesion was unaffected by the patt
ern of fibrinopeptide cleavage or by the removal of peptide beta 15-42
from fibrin. The results indicate that separate sites on the fibrin m
olecule mediate adhesion and spreading, and that the latter requires c
leavage of FPB and the new amino terminus of the beta chain. They furt
her suggest that cellular responses to fibrin are regulated by the pro
teolytic cleavages and conformational changes that convert fibrinogen
to fibrin and may also be modulated by plasmic or elastase degradation
.