Granulysin Expression in Lymphocytes that Populate the Peripheral Blood and the Myocardium after an Acute Coronary Event

Abstract

We aimed to analyse granulysin (GNLY)-mediated cytotoxicity in the peripheral blood of patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated with anti-ischaemic drug therapy. Thirty-nine NSTEMI patients with a median age of 70 years and 28 age-matched healthy subjects were enrolled in this study. On day 7 after MI, the number of GNLY(+) lymphocytes in the peripheral blood increased approximately six-fold of that in the healthy subjects, measured by flow cytometry. On day 14, the number of GNLY(+) cells significantly decreased in T, NKT, and both CD56(+dim) and CD56(+bright) NK subsets. GNLY(+) CD3(+) and GNLY(+) CD56(+) cells infiltrated central zone of myocardial infarction (MI). In persons who died in the first week after MI, GNLY(+) cells were found within accumulation of apoptotic leucocytes and reached the apoptotic cardiomyocytes in border MI zones probably due to the influence of interleukin-15 in peri-necrotic cardiomyocytes, as it is was shown by immunohistology. By day 28, the percentage of GNLY(+) lymphocytes in peripheral blood returned to the levels similar to that of the healthy subjects. Anti-GNLY mAb decreased apoptosis of K562 targets using peripheral blood NK cells from days 7 and 28 after MI, while in assays using cells from days 1 and 21, both anti-GNLY and anti-perforin mAbs were required to significantly decrease apoptosis. Using NK cells from day 14, K562 apoptosis was nearly absent. In conclusion, it seems that GNLY(+) lymphocytes, probably attracted by IL-15, not only participate partially in myocardial cell apoptosis, but also hasten resolution of cardiac leucocyte infiltration in patients with NSTEMI.