Molecular and Cellular BiologyMolecular Evidence for Induction of Intracellular Adhesion Molecule-1 in the Viable Border Zone Associated With Ischemia-Reperfusion Injury of the Dog Heart
作者:
Keith A. Youker,
Hal K. Hawkins,
Gilbert L. Kukielka,
Jerry L. Perrard,
Lloyd H. Michael,
Christie M. Ballantyne,
C. Wayne Smith,
Mark L. Entman,
期刊:
Circulation
(OVID Available online 1994)
卷期:
Volume 89,
issue 6
页码: 2736-2746
ISSN:0009-7322
年代: 1994
出版商: OVID
数据来源: OVID
摘要:
Background Acute inflammation may play a role in injury during reperfusion following myocardial ischemia. Studies in vitro suggest that intracellular adhesion molecule-1 (ICAM-1) mediates neutrophil adherence to cardiac myocytes and neutrophil-mediated injury. We have shown cytokine activity in postischemic cardiac lymph sufficient to maximally express ICAM-1 on myocytes and that ICAM-1 mRNA is found in the previously ischemic myocardium early in reperfusion.Methods and Results In the present study, we used in situ hybridization techniques to detect ICAM-1 mRNA and examine the cells of origin, relation to cell injury, and relation to inflammatory infiltration after 1 hour of ischemia and varying times of reperfusion. By 1 hour of reperfusion, ICAM-1 mRNA was detected in much of the ischemic myocardium, except in areas of contraction band necrosis. At 2 and 3 hours, a clear demarcation of necrotic areas surrounding ischemic areas of viable myocardium with ICAM-1 mRNA staining was present, and ICAM-1 mRNA staining increased with time. Nonischemic areas had no visible ICAM-1 mRNA staining in the first 3 hours. By 24 hours of reperfusion, ICAM-1 mRNA was present in both control and ischemic segments (excluding the necrotic areas) compatible with a generalized circulation of cytokines persistent at 24 hours. In the absence of reperfusion, ICAM-1 mRNA staining was not seen in the first 3 hours and was markedly reduced at 24 hours. The interface of viable and necrotic cells also contained the most extensive inflammatory infiltration.Conclusions Evidence is presented that induction of ICAM-1 mRNA has highly specific localization to ischemic but viable myocardium. Induction of ICAM-1 mRNA transcription in early reperfusion may render the viable "border zone" susceptible to neutrophil-induced injury. (Circulation. 1994;89:2736-2746.)
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