title: 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.
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: V
authors.initials: V
authors.lastname: Persic
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: A
authors.initials: A
authors.lastname: Ruzic
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: B
authors.initials: B
authors.lastname: Miletic
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: D Travica
authors.initials: DT
authors.lastname: Samsa
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Rakic
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: D
authors.initials: D
authors.lastname: Raljevic
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: V Pehar
authors.initials: VP
authors.lastname: Pejcinovic
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: S
authors.initials: S
authors.lastname: Eminovic
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: L
authors.initials: L
authors.lastname: Zaputovic
authors.affiliation: Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapija" Opatija, Opatija, CroatiaDepartment of Medical Rehabilitation, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Pathology, Medical Faculty, University of Rijeka, Rijeka, CroatiaDivision of Cardiology Clinical Hospital Center Rijeka, Rijeka, CroatiaDepartment of Internal Medicine, Medical Faculty, University of Rijeka, Rijeka, CroatiaDepartment of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: G
authors.initials: G
authors.lastname: Laskarin
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D018920:Coculture Techniques; D005260:Female; D015870:Gene Expression; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology* / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D032383:Myocytes, Cardiac / Q000276:immunology* / Q000473:pathology; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D054353:Perforin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D017252:CD3 Complex; D019002:CD56 Antigen; C075005:GNLY protein, human; C569274:IL15 protein, human; D019409:Interleukin-15; C522918:NCAM1 protein, human; D054353:Perforin