Neutrophil adherence to isolated adult cardiac myocytes. Induction by cardiac lymph collected during ischemia and reperfusion.

Abstract

Canine neutrophils can be induced to adhere in vitro to isolated adult cardiac myocytes by stimulation of the neutrophils with chemotactic factors such as zymosan-activated serum (ZAS) only if the myocytes have been previously exposed to cytokines such as interleukin 1 (IL-1) or tumor necrosis factor-a. These cytokines induce synthesis and surface expression ofintercellular adhesion molecule-i (ICAM-1) on the myocyte, and neutrophil adhesion is almost entirely CD18 and ICAM-1 dependent. The present study examines cardiac-specific lymph collected from awake dogs during i-h coronary occlusion and 3 d of reperfusion for its ability to induce both ICAM-1 expression in cardiac myocytes, and neutrophil-myocyte adherence. Reperfusion lymph induced ICAM-1 expression in isolated myocytes, and myocyte adherence to ZAS-stimulated neutrophils that was completely inhibited by anti-CD18 and anti-ICAM-i monoclonal antibodies. This activity peaked at 90 min of reperfusion and persisted for up to 72 h. Preischemic lymph was not stimulatory. IL-1 appeared not to be a stimulating factor in lymph in that dilutions of lymph were found to inhibit the stimulatory effects of recombinant IL-1it. However, investigation of interleukin 6 (IL-6) revealed that recombinant IL-6 stimulated myocyte adhesiveness for ZAS-stimulated neutrophils (ED90 = 0.002 U/ml) and expression of ICAM-1 by isolated myocytes. IL-6 neutralizing antibody markedly reduced the ability of reperfusion lymph to stimulate adhesion and ICAM-1 expression, and estimates of levels of IL-6 in reperfusion lymph ranged from 0.035 to 0.14 U/ml. These results indicate that cytokines capable of promoting neutrophil-myocyte adhesion occur in extracellular fluid during reperfusion of ischemic myocardium, and that one of these cytokines is IL-6. Neutrophilmyocyte adhesion may be of pathogenic significance because it may enhance the cytotoxic activity of the neutrophil. (J. Clin. Invest. 1992. 89:602-609.) Key words: cardiac lymph * cytokine induction * intercellular adhesion molecule-i * interleukin 6 * ischemia-reperfusion injury Introduction Numerous studies indicate that neutrophils contribute to myocardial cell injury after ischemia particularly under conditions

Cardiac Myocytes Produce Interleukin-6 in Culture and in Viable Border Zone of Reperfused Infarctions

“…This activity could be abolished by neutralizing antibodies to IL-6. 18 In the same model, we demonstrated that reperfusiondependent induction of ICAM-1 mRNA occurred in the viable myocytes of the border zone of myocardial infarction. 19 -21 Subsequent studies showed an induction of IL-6 in the myocardium of a canine model of ischemia and reperfusion.…”

IL-6 knock-out mice exhibit resistance to splanchnic artery occlusion shock

“…In addition, in vivo administration of antibodies raised against ICAM-1 reduced neutrophil infiltration into the inflamed lungs in the rabbit and protects the development of SAO-induced injury. Recently it has been shown that the adhesive mechanism can be directly stimulated by the ability of recombinant IL-6 to induce ICAM-1 on cardiac myocytes [43]. Therefore, IL-6 effects may extend beyond the induction of ligand-specific adhesion of neutrophil to cardiac myocytes.…”

Tumor-Necrosis-Factor-.ALPHA.-Gene-Deficient Mice Have Improved Cardiac Function Through Reduction of Intercellular Adhesion Molecule-1 in Myocardial Infarction

“…28 Postischemic cardiac lymph can induce expression of both ICAM-1 and interleukin-6, and treatment with anti-TNF-antibody inhibits its ability to do so. 3,29 TNFinitiates a cytokine cascade as the upstream cytokine and thereby induces the expression of ICAM-1. In the present study, ICAM-1 mRNA in the infarcted area was less in the KO mice at each time point and this reduced expression of ICAM-1 mRNA correlated with the temporal change of reduced infiltration of neutrophils into the infarcted myocardium.…”