PLASMA-MEDIATED NEUTROPHIL ACTIVATION DURING ACUTE MYOCARDIAL-INFARCTION - ROLE OF PLATELET-ACTIVATING-FACTOR

1. Polymorphonuclear neutrophils are involved in the development of my ocardial injury during ischaemia through the release of free oxygen ra dicals and by adhesion of activated polymorphonuclear neutrophils to e ndothelium, resulting in plugging of coronary capillaries. Polymorphon uclear neutrophil activation may be a result of contact with ligands e xpressed by endothelial cells and/or a response to soluble stimuli rel eased from ischaemic tissue to the plasma. 2. To investigate this we s tudied plasma-mediated polymorphonuclear neutrophil activation in vitr o using plasma samples collected from 14 patients with acute myocardia l infarction at time of admission and 6 h and 1, 2, 5 and 7 days later . Plasma samples were incubated with washed polymorphonuclear neutroph ils isolated from healthy donors. Expression of adhesion molecules CD1 8/CD11b integrin and L-selectin (Leu-8) were measured by flow cytometr y and superoxide anion production in polymorphonuclear neutrophils was measured by chemiluminescence. 3. Plasma samples obtained 66 and 1 da y after admission were capable of inducing CD18/CD11b antigen expressi on, superoxide anion production and L-selectin shedding in the washed polymorphonuclear neutrophils, and this effect was significant when co mpared with plasma taken at 5 and 7 days after admission. 4. The plasm a-mediated polymorphonuclear neutrophil stimulation was prevented when the PMN were pretreated antagonists activating factor concentrations detected in the plasma samples were not higher than those detected in plasma from healthy subjects. 5. These findings suggest that during ac ute myocardial infarction peripheral plasma contains soluble stimuli c apable of inducing polymorphonuclear neutrophil integrin expression, L -selectin shedding and oxygen free radical production and that platele t-activating factor appears to act as an autocrine polymorphonuclear n eutrophil stimulus.