Autacoid binding to serum proteins. Interaction of platelet activating factor (PAF) with human serum alpha-1-acid glycoprotein (AAG).

Platelet activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent bioactive phospholipid released from platelets, neutrophils, basophils and macrophages that has been proposed as a mediator of anaphylaxis, acute lung injury and other disorders. Specific factors which stabilize PAF and/or regulate PAF activity in body fluids are largely unknown. As part of a general autacoid-serum protein binding screen, the platelet activating factor-alpha-1-acid glycoprotein (PAF-AAG) interaction was indirectly characterized by examining the ability of PAF to displace propranolol from AAG. Both PAF and its deacetylated metabolite (lyso-PAF), at 20 microM, doubled the fraction unbound of propranolol (0.4 microM) from purified human AAG (20 microM). None of the other autacoids that were studied (epinephrine, serotonin, spermidine, putrescine, leu-enkephalin or phenethylamine) exhibited any propranolol displacement activity. Scatchard analysis indicated that PAF competitively displaced propranolol from AAG, causing the apparent affinity constant for propranolol-AAG to decrease from 1.8 X 10(5) M to 6.9 X 10(4) M. PAF behaved qualitatively like chlorpromazine (a documented inhibitor of propranolol binding to AAG), but PAF was less effective at displacing propranolol. The apparent binding to AAG may help stabilize and transport extracellular PAF. Furthermore, the interaction of PAF and AAG suggests that serum AAG, which fluctuates in a number of diseases, may function to regulate PAF activity during acute and chronic disease states.