Abstract
Our studies in 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.
Original language | English (US) |
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Pages (from-to) | 5-12 |
Number of pages | 8 |
Journal | Molecular and Cellular Biochemistry |
Volume | 147 |
Issue number | 1-2 |
DOIs | |
State | Published - Jun 1995 |
Keywords
- cell adhesion molecules
- interleukin-6
- interleukin-8
- myocardial infarction
- myocardial reperfusion injury
- neutrophils
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Clinical Biochemistry
- Cell Biology