Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium

Gilbert L. Kukielka, Hal K. Hawkins, Lloyd Michael, Anthony M. Manning, Keith Youker, Caryl Lane, Mark L. Entman, C. Wayne Smith, Donald C. Anderson

Research output: Contribution to journalArticlepeer-review

209 Scopus citations


Previous studies in vitro have shown an important role for intercellular adhesion molecule-1 (ICAM-1) in adherence interactions of canine neutrophils with canine jugular vein endothelial cells and in cytotoxicity of canine neutrophils for adult cardiac myocytes. To evaluate the regulation of ICAM-1 in myocardial inflammation and its role in the pathogenesis of myocardial ischemia and reperfusion, a series of in vivo and ex vivo studies were performed in canine animals. Systemic administration of LPS elicited ICAM-1 mRNA in several tissues, including myocardium, which demonstrated increasing ICAM-1 staining on intercalated discs of cardiac myocytes. In ischemia and reperfusion protocols: (a) ICAM-1 mRNA was found in ischemic segments within 1 h of reperfusion and in both ischemic and normally perfused segments by 24 h of reperfusion; (b) expression of ICAM-1 was detected in cardiac myocytes in the ischemic region by 6 h of reperfusion; increased expression was seen thereafter as a function of time; (c) post-ischemic (but not preischemic) cardiac lymph collected at intervals from 1 to 24 h after reperfusion elicited ICAM-1 mRNA, ICAM-1 expression, and ICAM-1-dependent neutrophil adhesion in canine jugular vein endothelial cells and in cardiac myocytes with peak cytokine activity seen by 1 h; (d) extravascular localization of neutrophils was detected in ischemic areas only, and was associated with endothelium bearing high levels of ICAM-1 within 1 h of reperfusion; infiltration increased thereafter in association with increasing levels of ICAM-1 mRNA in myocardial segments and increasing levels of ICAM-1 expression on cardiac myocytes. These findings provide the first direct evidence for inflammatory regulation of ICAM-1 in ischemic and reperfused canine myocardium. They support the hypothesis that ICAM-1 participates in neutrophil-mediated myocardial damage.

Original languageEnglish (US)
Pages (from-to)1504-1516
Number of pages13
JournalJournal of Clinical Investigation
Issue number3
StatePublished - Sep 1993
Externally publishedYes


  • Cell adhesion molecules
  • Inflammation
  • Myocardial infarction
  • Myocardial ischemia and reperfusion injury
  • Neutrophil

ASJC Scopus subject areas

  • General Medicine


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