Neutralization of heparin-related saccharides by XXXX -rich glycoprotein and platelet factor 4.

@entity1 @entity1707 @entity14024 @entity3793 @entity1735 @entity17241 @entity60641 @entity38796 @entity5582 @entity6236 @entity597
Heparin and heparin oligosaccharides prepared by @entity17241 depolymerization were fractionated by affinity chromatography on immobilized @entity5582 and by gel chromatography. The anticoagulant activities of high affinity heparin of Mr greater than or equal to 7,800 could be readily neutralized by the plasma protein @entity3793 -rich glycoprotein (see also Lijnen, H.R., Hoylaerts, M., and Collen, D. (1983) J. Biol. Chem. 258, 3803-3808), whereas oligosaccharides falling below 18 @entity1735 units (Mr 5,400) became increasingly resistant to neutralization. An @entity60641 with characteristic marked ability to accelerate the inactivation of @entity6236 by @entity5582 retained greater than 50% of its activity even at a @entity3793 -rich glycoprotein/oligosaccharide molar ratio of 500:1. @entity3793 -rich glycoprotein, like the platelet-derived heparin neutralizing protein platelet factor 4 (Lane, D.A., Denton, J., Flynn, A.M., Thunberg, L. and Lindahl, U. (1984) Biochem J. 218, 725-732), therefore requires interaction with @entity1735 sequences in addition to the @entity5582 -binding pentasaccharide of heparin in order to efficiently express its antiheparin activity. Heparan @entity597 isolated from @entity1707 intestinal mucosa ( @entity38796 , Mr approximately 20,000) and from @entity1 aorta (HS II, Mr approximately 40,000) exhibited anti- @entity6236 activities of 180 and 20 units/micromol [corrected], respectively. A fraction corresponding to about 5% of @entity38796 bound with high affinity to immobilized @entity5582 and contained all of the anticoagulant activity of the starting material. While these heparan @entity14024 were readily neutralized by platelet factor 4, they were relatively resistant to neutralization by @entity3793 -rich glycoprotein, although complete neutralization could be attained in the presence of molar excess of this protein. These findings may be of importance in relation (a) to the functional role of endogenous anticoagulant polysaccharides at the vascular wall and (b) to clinical situations in which heparin or heparin-related compounds are administered as exogenous anticoagulants.
