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Role of early reperfusion in the induction of adhesion molecules and cytokines in previously ischemic myocardium

  • Part I: Extracellular Matrix and Cardiocyte Interaction
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Abstract

Our studiesin vitro demonstrate that neutrophil mediated injury of isolated cardiac myocytes requires the presence of ICAM-1 on the surface of the myocyte and CD11b/CD18 activation on the neutrophil. In post-ischemic cardiac lymph, there is rapid appearance of C5a activity during the first hours of reperfusion. Interleukin-6 activity is present throughout the first 72 h of reperfusion and is sufficient to induce ICAM-1 on the surface of the cardiac myocyte.In situ hybridization studies suggest that ICAM-1 mRNA is found in viable myocardial cells on the edge of the myocardial infarction within 1 h of reperfusion. ICAM-1 protein expression on cardiac myocytes is seen after 6 h of reperfusion, and increases thereafter. Non-ischemic tissue demonstrates no early induction of ICAM-1 mRNA or ICAM-1 protein on myocardial cells. In our most recent experiments, we have determined that reperfusion is an absolute requirement for the early induction of myocardial ICAM-1 mRNA in previously ischemic myocardial cells. To further assess this, we have cloned and sequenced a canine interleukin-6 (IL-6) cDNA. The data suggest that early induction of IL-6 mRNA is also reperfusion dependent as it could be demonstrated in the same ischemic and reperfused segments in which ICAM-1 mRNA was found. Peak expression of IL-6 mRNA occurred much earlier than that for ICAM-1 mRNA. Similar experiments were then performed with a molecular probe for interleukin-8 (IL-8). This chemokine is a potent neutrophil stimulant and has a higher degree of specificity for neutrophils than classic chemoattractants such as C5a. The results suggest a similar pattern of induction that occurs within the first hour and is markedly, increased by reperfusion. The relationship of reperfusion to ICAM-1 and cytokine induction is discussed.

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Authors and Affiliations

  1. Section of Cardiovascular Sciences, Department of Medicine, The Methodist Hospital, Baylor College of Medicine, One Baylor Plaza, 77030-34988, Houston, TX, USA

    Gilbert L. Kukielka, Keith A. Youker, Lloyd H. Michael, Ajith G. Kumar, Christie M. Ballantyne, C. Wayne Smith & Mark L. Entman

  2. The DeBakey Heart Center, Speros P. Martel Section of Leukocyte Biology, Department of Pediatrics and Texas Children's Hospital, Baylor College of Medicine, One Baylor Plaza, 77030-34988, Houston, TX, USA

    Gilbert L. Kukielka, Keith A. Youker, Lloyd H. Michael, Ajith G. Kumar, Christie M. Ballantyne, C. Wayne Smith & Mark L. Entman

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  1. Gilbert L. Kukielka
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  2. Keith A. Youker
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  7. Mark L. Entman
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Kukielka, G.L., Youker, K.A., Michael, L.H. et al. Role of early reperfusion in the induction of adhesion molecules and cytokines in previously ischemic myocardium. Mol Cell Biochem 147, 5–12 (1995). https://doi.org/10.1007/BF00944777

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