Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo.

Abstract

Neutrophil adhesion and direct cytotoxicity for cardiac myo-cytes require chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was cloned and the mature recombinant protein expressed in Escherichia coli BL21 cells. Recombinant canine IL-8 markedly increased adhesion of neutrophils to isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity for cardiac myocytes. Both processes were specifically blocked by antibodies directed against CD18 and IL-8. In vivo, after 1 h of coronary occlusion, IL-8 mRNA was markedly and consistently induced in reperfused segments of myocardium. IL-8 mRNA was not induced in control (normally perfused) myocardial segments. Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without reperfusion. Highest levels of induction were evident in the most ischemic myocardial segments. IL-8 mRNA peaked in the first 3 h of reperfusion and persisted at high levels beyond 24 h. IL-8 staining was present in the inflammatory infiltrate near the border between necrotic and viable myocardium, as well as in small veins in the same area. These findings provide the first direct evidence for regulation of IL-8 in ischemic and reperfused canine myocardium and support the hypothesis that IL-8 participates in neutrophil-mediated myocardial injury. (J. Clin. Invest. 1995. 95:89-103.)

Pancreatic Duct Cells in Human Islet Cell Preparations Are a Source of Angiogenic Cytokines Interleukin-8 and Vascular Endothelial Growth Factor

“…They were even detected in the circulation of these animals, be it only during the first day posttransplantation. This short episode of elevated circulating levels does not exclude that both proteins remain produced and locally released at later times but indicates that the immediate posttransplant period favors their release, possibly as an effect of the hypoxic and/or inflammatory environment, which is known to induce IL-8 and VEGF production (26,27). When comparing data from independent experiments, we observed a high variation in the mRNA expression level of both proteins.…”

Inhibition of CINC-1 Decreases Right Ventricular Damage Caused by Experimental Pulmonary Embolism in Rats

“…Multiple factors initiate LV inflammation, including complement activation (38), reactive oxygen species generation (39), cytokines (40), and chemokines (41,42). Neutrophils contribute to cardiac myocyte damage in LV ischemia by releasing reactive oxygen species, proteases, cytokines, vasoconstricting lipids, and up-regulating adhesion molecules (35).…”

Roles and Relationship of Macrophages and Monocyte Chemotactic and Activating Factor/Monocyte Chemoattractant Protein-1 in the Ischemic and Reperfused Rat Heart

“…Histopathologically, it has been shown that neutrophils first penetrate the infarcted myocardium, followed by macrophages, and it has been reported that neutrophils are associated with reperfusion injury, in concert with the induction of intracellular adhesion molecule-1 (ICAM-1), interleukin (IL)-6, or IL-8 (Hawkins et al, 1996;Kukielka et al, 1993Kukielka et al, , 1995aKukielka et al, , 1995bNeumann et al, 1995;Youker et al, 1994). It has also been reported that reperfusion is associated with an increase in the number of macrophages compared with the nonreperfused Mean number of macrophages in the hearts at 1 hour, 3 hours, and 6 hours after reperfusion (R).…”