AJP - Heart and Circulatory Physiology, Vol 250, Issue 5 879-H888, Copyright © 1986 by American Physiological Society
Anticoagulantly active heparin-like molecules from mast cell-deficient mice
J. A. Marcum, J. B. McKenney, S. J. Galli, R. W. Jackman and R. D. Rosenberg
To assess the contribution of mast cells to the maintenance of blood
fluidity, the hindlimb vasculature of mast cell-deficient mice (W/Wv) and
littermates containing normal levels of mast cells (+/+), were perfused
with purified human thrombin and antithrombin. Enzyme-inhibitor complex
generation within the vasculature was enhanced to a comparable extent for
W/Wv and +/+ mice over the uncatalyzed rate, that level of complex produced
within a similar time interval in the absence of heparin. Perfusion of
purified Flavobacterium heparinase prior to infusion of the hemostatic
components, or perfusion of antithrombin modified at the heparin-binding
domain, reduced W/Wv and +/+ hindlimb thrombin-antithrombin complex
formation to the uncatalyzed rate. To further define the cellular source of
the vascular-associated heparin-like molecules, endothelial cells isolated
from epididymal fat pads of W/Wv and +/+ mice were grown in vitro. The
acceleration of thrombin-antithrombin interactions in the presence of
endothelial cell-derived glycosaminoglycans was similar for W/Wv and +/+
mice, was abolished with purified bacterial heparinase, and was expressed
to only a minor extent when utilizing modified antithrombin. The
biologically active mucopolysaccharides appear to be present on the cell
surface.
