Heparin binds to human monocytes and modulates their procoagulant activities and secretory phenotypes. Effects of histidine-rich glycoprotein.
The binding of heparin to human monocytes and the monocytoid cell line U937 was characterized. Heparin binding was rapid, specific, saturable, and reversible. There was a single class of heparin binding sites, with an apparent dissociation constant of 0.19 mumol/L and 1.9 x 10(6) sites per cell. The binding was not dependent on the anticoagulant property of heparin. Analysis of surface-iodinated cell lysates by heparin affinity chromatography revealed a major 120 Kd cell surface heparin-binding protein. Histidine-rich glycoprotein, a potent heparin antagonist found in human plasma and platelets, decreased the affinity of heparin for cell binding. Cell surface bound heparin was functionally active and markedly accelerated the inactivation of thrombin by antithrombin III. Heparin induced the release of two monocyte secretory proteins of 160 and 17 Kd. Our study supports the thesis that heparin and related glycosaminoglycans interact with monocytes and macrophages, as well as endothelial cells and smooth muscle cells, and play an important and complex role in blood vessel wall biology.
Leung
L
L
Department of Medicine, Stanford University School of Medicine, CA 94305.
Saigo
K
K
Grant
D
D
D001665:Binding Sites; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002460:Cell Line; D005591:Chemical Fractionation; D006023:Glycoproteins / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000302:isolation & purification; D009000:Monocytes / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D011506:Proteins / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate; D013917:Thrombin / Q000037:antagonists & inhibitors; D000099053:Histidine-Rich Glycoprotein
D001779:Blood Coagulation Factors; D006023:Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; C045071:leukocyte procoagulant activity; D006493:Heparin; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate