Transcardiac release of leukotriene C4by neutrophils in patients with coronary artery disease

Abstract

Leukotriene C4is a potent constrictor of smooth muscle in vitro and may induce coronary vasoconstriction in vivo. To study leukotriene C4release by neutrophils in patients with coronary artery disease, neutrophils were separated from blood samples taken from the coronary sinus and aorta in 20 patients with stable exertional angina and angiographically documented coronary artery narrowings (group I). Eight patients with normal coronary arteries were also studied (group II).To assess leukotriene C4generation, neutrophils were incubated with calcium ionophore A 23187 (0.25 μM) and the supernatants obtained after centrifugation were analyzed for leukotriene C4by radioimmunoassay.Patients in group I had a significantly lower release of leukotriene C4from neutrophils separated from the coronary sinus blood than from those separated from aortic blood (4.33 ± 0.69 versus 5.92 ± 0.54 ng/ml, p < 0.025), whereas patients in group II had a similar rekase of kukotriene C4by the neutrophils separated from coronary sinus blood and from aortic blood (6.0 ± 0.72 versus 6.4 ± 0.66 ng/ml, p = NS). Moreover, in group I patients, a significant correlation was found (p < 0.01) between the extent of coronary artery disease (expressed by the Leaman coronary score) and the percent reduction in leukotriene C4released from neutrophils separated from coronary sinus blood as compared with leukotriene C4produced by neutrophils separated from aortic blood.These data show that neutrophils from patients with coronary artery disease have a reduced ability to produce leukotriene C4after stimulation by calcium ionophore A 23187. The release of leukotriene C4from neutrophils passing through a diseased coronary tree may contribute to the development of the inappropriate vasoconstriction associated with the endothelial dysfunction of atherosclerotic coronary vessels.