Fibrinogen binding to purified platelet glycoprotein IIb-IIIa (integrin alpha IIb beta 3) is modulated by lipids.
Soluble fibrinogen binding to the glycoprotein IIb-IIIa complex (integrin alpha IIb beta 3) requires platelet activation. The intracellular mediator(s) that convert glycoprotein IIb-IIIa into an active fibrinogen receptor have not been identified. Because the lipid composition of the platelet plasma membrane undergoes changes during activation, we investigated the effects of lipids on the fibrinogen binding properties of purified glycoprotein IIb-IIIa. Anion exchange chromatography of lipids extracted from platelets exposed to thrombin or other platelet agonists resolved an activity that increased fibrinogen binding to glycoprotein IIb-IIIa. A monoester phosphate was important for activity, and phosphatidic acid coeluted with the peak of activity. Purified phosphatidic acid dose-dependently promoted a specific interaction between glycoprotein IIb-IIIa and fibrinogen which possessed many but not all of the properties of fibrinogen binding to activated platelets. Phosphatidic acid appeared to increase the proportion of fibrinogen binding-competent glycoprotein IIb-IIIa complexes without altering their affinity for fibrinogen. The effects of phosphatidic acid were a result of specific structural properties of the lipid and were not mimicked by other phospholipids. Lysophosphatidic acid, however, was a potent inducer of fibrinogen binding to glycoprotein IIb-IIIa. These results demonstrate that specific lipids can affect fibrinogen binding to purified glycoprotein IIb-IIIa and suggest that the lipid environment has the potential to influence fibrinogen binding to its receptor.
Smyth
S S
SS
Department of Pharmacology, University of North Carolina, Chapel Hill 27599.
Hillery
C A
CA
Parise
L V
LV
D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002846:Chromatography, Affinity; D002848:Chromatography, DEAE-Cellulose; D002855:Chromatography, Thin Layer; D004075:Diglycerides / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism*; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008563:Membrane Lipids / Q000097:blood* / Q000302:isolation & purification; D010712:Phosphatidic Acids / Q000097:blood / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D004075:Diglycerides; D005994:Glycerophosphates; D008563:Membrane Lipids; D010712:Phosphatidic Acids; D010743:Phospholipids; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen; D013755:Tetradecanoylphorbol Acetate