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Research Article Free access | 10.1172/JCI117680

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

G L Kukielka, C W Smith, G J LaRosa, A M Manning, L H Mendoza, T J Daly, B J Hughes, K A Youker, H K Hawkins, L H Michael, A Rot, and M L Entman

Section of Cardiovascular Sciences, Methodist Hospital, DeBakey Heart Center, Houston, Texas.

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Section of Cardiovascular Sciences, Methodist Hospital, DeBakey Heart Center, Houston, Texas.

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Section of Cardiovascular Sciences, Methodist Hospital, DeBakey Heart Center, Houston, Texas.

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Section of Cardiovascular Sciences, Methodist Hospital, DeBakey Heart Center, Houston, Texas.

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Section of Cardiovascular Sciences, Methodist Hospital, DeBakey Heart Center, Houston, Texas.

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Section of Cardiovascular Sciences, Methodist Hospital, DeBakey Heart Center, Houston, Texas.

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Section of Cardiovascular Sciences, Methodist Hospital, DeBakey Heart Center, Houston, Texas.

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Section of Cardiovascular Sciences, Methodist Hospital, DeBakey Heart Center, Houston, Texas.

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Published January 1, 1995 - More info

Published in Volume 95, Issue 1 on July 21, 2021
J Clin Invest. 2021;95(1):89–103. https://doi.org/10.1172/JCI117680.
© 1995 The American Society for Clinical Investigation
Published January 1, 1995 - Version history
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Abstract

Neutrophil adhesion and direct cytotoxicity for cardiac myocytes 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.

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Version history
  • Version 1 (January 1, 1995): No description
  • Version 2 (July 21, 2021): Added A. Rot and M.L. Entman to the author list.

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Referenced in 9 patents
59 readers on Mendeley
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