Anticoagulantly active heparin-like molecules from mast cell-deficient mice

Abstract

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.

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

“…Heparinase treatment: Endogenous endothelial surface layer heparinate groups participate in diverse flow-induced responses [10,11,13,31], and these numerous groups can be exclusively and selectively hydrolyzed with intravascular heparinase [39][40][41][42][43]. To minimize the possibility of transendothelial diffusion, heparinase was administered repeatedly using a low concentration gradient and very short exposure times [8,11,13,31,44].…”

“…After a transient infusion, the oligosaccharide polymer remains bound to the luminal endothelial membrane as shown by confocal microscopy, even after extensive washout. Upon binding [31,43,[46][47][48][49]. Thus, oligosaccharide polymer, after binding to endothelial surface layer lectins such as the bradykinin B2 receptor, likely competes for binding with endogenous oligosaccharides.…”

The physiologic and therapeutic role of Heparin in implantation and placentation

“…Moreover, its true physiological role in the body remains uncertain, since blood anticoagulation is achieved mostly by heparan sulfate proteoglycans derived from endothelial cells 3 . Heparin is usually stored within the mast cells secretory granules and released only into the vasculature at sites of tissue injury.…”

Overview on Biocompatibilities of Implantable Biomaterials

“…Blood anti-coagulation is usually achieved by heparan sulfate proteoglycans which derive from endothelial cells stored within the secretory granules of mast cells and only released into the vasculature at sites of tissue injury [107]. Rather than anticoagulation, the main role of heparin may be defense at such sites against invading bacteria and other foreign materials [108].…”