Modulation of the random migration of human platelets.

Random migration of human platelets has been recognized as a parameter of platelet function which can be assessed in a reproducible manner by modification of the Boyden micropore filter technique for evaluating this function in other cells (Boyden, S. 1962. J. Exp. Med. 115: 453-466). Because platelets are extremely susceptible to aggregation, the conditions for collecting and isolating platelets and the migration buffer (Ca(++) and Mg(++)-free phosphate buffered saline, pH 6.8, with glucose and gelatin) were selected to minimize such a possibility. The random movement of platelets into the micropore filter was maximal at 30-37 degrees C and was contingent upon the metabolic integrity of the cell; thus, it can be attributed to active spontaneous migration. While the initiating and enhancing effects of epinephrine on the platelet aggregation-release reaction are mediated by an alpha-adrenergic receptor, the inhibition of random migration involved a beta-receptor. Equimolar propranolol but not phentolamine prevented epinephrine inhibition of random migration, and isoproterenol had activity comparable to epinephrine while phenylephrine was inactive. The capacity of the cholinomimetic agent, carbachol, to increase platelet migration is reminiscent of the recent findings in several cell systems in which beta-adrenergic and cholinergic stimuli have opposite effects. The prostaglandins E1 and E2 augmented spontaneous migration in contrast to their well established inhibitory action on platelet aggregation at the concentrations employed. The suppression by indomethacin of prostaglandin enhancement and of spontaneous migration implies a requirement for the prostaglandin biosynthetic pathway during the migration process. Thus, the spontaneous migration of human platelets, an additional parameter of platelet function for in vitro investigations, disclosed not only a beta-adrenergic receptor for epinephrine, but also a capacity for cholinergic augmentation and an apparent requirement for prostaglandin biosynthesis.