Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion.
Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates. Platelets were allowed to adhere and the amount of adhesion detected enzymatically. The LPA and adrenaline combination induced a synergistic increase of platelet adhesion to a normally non-adhesive albumin surface. The degree of synergy varied markedly between individuals; these variations could not be explained by age, gender, blood type or different amounts of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma. There was a trend indicating increased synergistic effect for platelets sensitive to adrenaline stimulation. The synergistic effect was blocked by the alpha2-adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system creatine phosphate/creatine phosphokinase and antibodies against alphaIIbbeta3. Furthermore, platelets adhering to albumin after adrenaline and LPA treatment expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to increase alphaIIbbeta3-mediated platelet adhesion to albumin, dependent on alpha2-adrenoceptor signalling and platelet secretion. We also confirm that synergistic platelet activation achieved with LPA and adrenaline is highly donor dependent.
Eriksson
Andreas C
AC
Division of Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, Sweden. ander@imv.liu.se
Whiss
Per A
PA
Nilsson
Ulrika K
UK
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000418:Albumins / Q000378:metabolism / Q000502:physiology*; D001323:Autoantibodies / Q000502:physiology; D001782:Blood Donors; D001792:Blood Platelets / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D019007:P-Selectin / Q000096:biosynthesis; D010973:Platelet Adhesiveness / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D015016:Yohimbine / Q000494:pharmacology
D000418:Albumins; D001323:Autoantibodies; D008246:Lysophospholipids; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D015016:Yohimbine; D000244:Adenosine Diphosphate; C032881:lysophosphatidic acid; D004837:Epinephrine