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

Abstract

Leukotriene C4 is a potent constrictor of smooth muscle in vitro and may induce coronary vasoconstriction in vivo. To study leukotriene C4 release 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 C4 generation, neutrophils were incubated with calcium ionophore A 23187 (0.25 microM) and the supernatants obtained after centrifugation were analyzed for leukotriene C4 by radioimmunoassay. Patients in group I had a significantly lower release of leukotriene C4 from 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 less than 0.025), whereas patients in group II had a similar release of leukotriene C4 by 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 less than 0.01) between the extent of coronary artery disease (expressed by the Leaman coronary score) and the percent reduction in leukotriene C4 released from neutrophils separated from coronary sinus blood as compared with leukotriene C4 produced by neutrophils separated from aortic blood. These data show that neutrophils from patients with coronary artery disease have a reduced ability to produce leukotriene C4 after stimulation by calcium ionophore A 23187.(ABSTRACT TRUNCATED AT 250 WORDS)

Sulfido‐peptide leukotrienes in coronary heart disease – relationship with disease instability and myocardial ischaemia

“…Our finding of increased sulfido-peptide LT production in association with clinical conditions characterized by plaque disruption and dynamic thrombosis is consistent with several lines of evidence of leucocyte activation in acute coronary syndromes [30][31][32], and with more recent reports of neutrophil-platelet interactions, as detected by flow-cytometry, in unstable angina [33,34].…”

C-Reactive Protein Increase in Unstable Coronary Disease

“…Our group has reported some of the earliest observations on leukocyte function and inflammation in coronary artery disease (7)(8)(9)(10)(11), showing an increase of the leukocyte CD11b/CD18 receptor (a glycoprotein complex involved in the adhesion process of neutrophils and monocytes to endothelial cells) in the coronary sinus of patients with unstable angina, substantiating the hypothesis that an inflammatory component plays a role in the pathogenesis of this clinical manifestation (10 -11). This observation stimulated further studies aimed at assessing the mechanism underlying the inflammatory outburst in such patients (12,13).…”

Phagocyte activation in coronary artery disease

“…Twenty ml of dextran 6% were added to bMod samples which were immediately placed on a CO 2 incubator at 37°C. The polymorphonuclear leukocytes were purified by means of the Isopaque-Ficoll system [5]. Cell viability was > 95% as measured by trypan blue exclusion or release of the cytoplasmatic enzyme lactic dehydrogenase.…”

“…Granulocytes were suspended in modified phosphate buffer saline (PBS) containing MgCI 2 0.7 mM, CaC12 1.4 mM and glucose 5 mM. Granulocyte suspension (3 x 106 cells/ml) was stirred at 37°C for 3 min in a siliconized glass cuvette; 0.1 ml Ca 2÷ ionophore A 23187 (final concentration 1 x 10-SM) (Sigma Chemicals, St. Louis, MO) was then added to 0.4 ml of PMN suspension, as aggregating agent, as previously reported [5].…”

“…Moreover, PMNs' aggregation may cause leukostatic plugs leading to microvascular occlusion [4]. Recent experimental and clinical observations have begun to define the molecular antigenic determinants on the surface of leukocytes which contribute to the adhesion process [4][5][6]. These studies have established the critical role in vivo of CDll/CD18 leukocyte adhesion molecules, a family of cell-surface glycoproteins consisting of three heterodimers, sharing a common /3-subunit with a distinct a-subunit (CDlla, CDllb, CDllc).…”