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In vitro activation of the contact (Hageman factor) system of plasma by
heparin and chondroitin sulfate E
Y Hojima, CG Cochrane, RC Wiggins, KF Austen and RL Stevens
A large number of negatively charged macromolecules, including DNA,
glycosaminoglycans, and proteoglycans, were tested as possible activators
of the contact (Hageman factor) system in vitro. Activation was assessed by
conversion of prekallikrein to kallikrein, as determined by amidolytic
assay and by cleavage of 125I-Hageman factor into 52,000- and 28,000-dalton
fragments. Of particular interest to these studies, heparin proteoglycan
and glycosaminoglycan from rat peritoneal mast cells, and squid chondroitin
sulfate E, which is representative of the glycosaminoglycan from cultured
mouse bone marrow derived mast cells, induced the reciprocal activation
between Hageman factor and prekallikrein. In addition, naturally occurring
heparin glycosaminoglycans from pig mucosa, bovine lung, and rat mast cells
also induced activation. In contrast, native connective tissue matrix
glycosaminoglycans and proteoglycans from several sources were inactive,
although when one such chondroitin sulfate was further sulfated in vitro,
it gained activity. When the negative charge of the activating agents was
blocked by the addition of hexadimethrine bromide, the cleavage of
125I-Hageman factor in the presence of prekallikrein was prevented. The
active negatively charged macromolecules induced cleavage of 125I-high
molecular weight kininogen in normal plasma but not in Hageman
factor-deficient or prekallikrein- deficient plasmas. Reconstitution of
prekallikrein-deficient plasma with purified prekallikrein restored the
kininogen cleavage upon addition of the active proteoglycans. These results
suggest that both heparin from connective tissue mast cells and highly
sulfated chondroitin sulfate E from cultured mouse bone marrow derived mast
cells (which are considered synonomous with mucosal mast cells) could
activate the contact system of plasma subsequent to an activation secretion
response.
Volume 63,
Issue 6,
pp. 1453-1459,
06/01/1984
Copyright © 1984 by The American Society of Hematology
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