Perforin-Mediated Cytotoxicity in non-ST Elevation Myocardial Infarction

Abstract

The aim of this investigation was to examine the role of perforin (P)-mediated cytotoxicity in the dynamics of tissue damage in patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated with anti-ischaemic drugs. We enrolled 48 patients with NSTEMI in this study [age, 71.5years; 61.5/76 (median, 25th/75th percentiles)]. The percentage of total peripheral blood P + lymphocytes was elevated owing to the increased frequency of P + cells within natural killer (NK) subsets, T and NKT cells in patients on day 1 after NSTEMI when compared with healthy controls. Positive correlations were found between cardiac troponin I plasma concentrations and the frequency of P + cells, P + T cells, P + NK cells and their CD56 +dim and CD56 +bright subsets during the first week after the NSTEMI. The expression of P in NK cells was accompanied by P-mediated cytotoxicity against K-562 targets at all days examined, except day 21, when an anti-perforin monoclonal antibody did not completely abolish the killing. The percentage of P + T cells, P + NKT cells and P + NK subsets was the highest on the day 1 after NSTEMI and decreased in the post-infarction period. CD56 + lymphocytes were found in damaged myocardium, suggesting their tissue recruitment. In conclusion, patients with NSTEMI have a strong and prolonged P-mediated systemic inflammatory reaction, which may sustain autoaggressive reactions towards myocardial tissue during the development of myocardial infarction. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.