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Calin from Hirudo medicinalis, an inhibitor of von Willebrand factor
binding to collagen under static and flow conditions
J Harsfalvi, JM Stassen, MF Hoylaerts, E Van Houtte, RT Sawyer, J Vermylen and H Deckmyn
Center for Molecular and Vascular Biology, University of Leuven, Belgium.
Calin from the saliva of the medicinal leech, Hirudo medicinalis, is a
potent inhibitor of collagen mediated platelet adhesion and activation. In
addition to inhibition of the direct platelet-collagen interaction, we
presently demonstrate that binding of von Willebrand to coated collagen can
be prevented by Calin, both under static and flow conditions in agreement
with the occurrence of binding of Calin to collagen, confirmed by
Biospecific Interaction Analysis. To define whether Calin acted by
inhibiting the platelet-collagen or the platelet- von Willebrand factor
(vWF)-collagen-mediated thrombus formation, platelet adhesion to different
types of collagens was studied in a parallel-plate flow chamber perfused
with whole blood at different shear rates. Calin dose-dependently prevented
platelet adhesion to the different collagens tested both at high- and
low-shear stress. The concentration of Calin needed to cause 50% inhibition
of platelet adhesion at high-shear stress was some fivefold lower than that
needed for inhibition of vWF-binding under similar conditions, implying
that at high-shear stress, the effect of Calin on the direct platelet-
collagen interactions, suffices to prevent thrombus formation. Platelet
adhesion to extracellular matrix (ECM) of cultured human umbilical vein
endothelial cells was only partially prevented by Calin, and even less so
at a high-shear rather than a low-shear rate, whereas the platelet binding
to coated vWF and fibrinogen were minimally affected at both shear rates.
Thus, Calin interferes with both the direct platelet- collagen interaction
and the vWF-collagen binding. Both effects may contribute to the inhibition
of platelet adhesion in flowing conditions, although the former seems to
predominate.
Volume 85,
Issue 3,
pp. 705-711,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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