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

Gilbert L. Kukielka, C. Wayne Smith, Gregory J. LaRosa, Anthony M. Manning, Leonardo H. Mendoza, Thomas J. Daly, Bonnie J. Hughes, Keith A. Youker, Hal K. Hawkins, Lloyd H. Michael, Antal Rot, Mark L. Entman

Research output: Contribution to journalArticle

197 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)89-103
Number of pages15
JournalJournal of Clinical Investigation
Volume95
Issue number1
DOIs
StatePublished - Jan 1995

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Keywords

  • cell adhesion molecules
  • chemotaxis
  • myocardial infarction
  • myocardial reperfusion injury
  • neutrophils

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kukielka, G. L., Smith, C. W., LaRosa, G. J., Manning, A. M., Mendoza, L. H., Daly, T. J., Hughes, B. J., Youker, K. A., Hawkins, H. K., Michael, L. H., Rot, A., & Entman, M. L. (1995). Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo. Journal of Clinical Investigation, 95(1), 89-103. https://doi.org/10.1172/JCI117680