Neutralization of the anticoagulant effects of glycosaminoglycans by serum amyloid P component: comparison with other plasma and platelet proteins.
Serum amyloid P protein (SAP) is a heparin-binding protein that is found in blood and connective tissues including some types of vascular basement membrane. In this article we present evidence that SAP is capable of blocking the anticoagulant effects of glycosaminoglycans. SAP neutralized the catalytic effect of heparin on the thrombin-antithrombin III reaction more effectively than vitronectin, histidine-rich glycoprotein, fibronectin, and high-molecular-weight kininogen and almost as effectively as platelet factor 4. SAP also blocked the effects of heparin and dermatan sulfate on the inhibition of thrombin by heparin cofactor II. We found evidence for the formation of a high-affinity 1:1 complex between SAP and heparin and for inhibition of binding of both thrombin and antithrombin III to heparin-Sepharose by SAP. We conclude that SAP may account for much of the heparin-neutralizing capacity of plasma under some conditions and that basement-membrane-bound SAP may modulate extravascular coagulation by blocking the anticoagulant effects of basement membrane glycosaminoglycans.
Williams
E C
EC
Department of Medicine, University of Wisconsin, Madison 53706.
Huppert
B J
BJ
Asakura
S
S
D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000737:chemistry*; D001798:Blood Proteins / Q000032:analysis / Q000494:pharmacology*; D003871:Dermatan Sulfate / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry; D005353:Fibronectins / Q000494:pharmacology; D005453:Fluorescence; D006023:Glycoproteins / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000097:blood / Q000494:pharmacology*; D006493:Heparin / Q000097:blood / Q000494:pharmacology; D015844:Heparin Cofactor II / Q000378:metabolism; D006801:Humans; D007704:Kininogens / Q000494:pharmacology; D010978:Platelet Factor 4 / Q000494:pharmacology; D011485:Protein Binding; D000683:Serum Amyloid P-Component / Q000032:analysis* / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D019096:Vitronectin
D000925:Anticoagulants; D001798:Blood Proteins; D005353:Fibronectins; D006023:Glycoproteins; D006025:Glycosaminoglycans; D007704:Kininogens; D000683:Serum Amyloid P-Component; D019096:Vitronectin; D003871:Dermatan Sulfate; D010978:Platelet Factor 4; D015844:Heparin Cofactor II; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin