Апоптоз нейтрофилов как параметр воспалительной реакции при патологии различного генеза

Polymorphonuclear leukocyte apoptosis as parameter of inflammatory reaction in the pathology of different genesis

With a half-life of 8-20 hours, PMNs are short-lived cells. In the absence of inflammatory stimuli, PMNs undergo genetically programmed cell death, or apoptosis, characterized by cytoplasmic shrinkage, nuclear condensation, membrane blebbing, DNA fragmentation, and formation of apoptotic bodies. Trimetazidine (TMZ) concerns to a new class of the preparations influencing a cellular metabolism and possessing antioxidation activity. Mechanisms of action of this preparation are actively studied. This study determined polymorphonuclear neutrophils apoptosis and its underlying mechanisms in controls (C), patients with stable (SAP) or unstable angina (UAP), and with acute myocardial infarction (AMI). Blood was drawn from 15 subjects of each C, SAP, UAP, and AMI. Apoptosis was measured by flow cytometry in isolated PMN (propidium iodide staining) and PMN from whole blood. Enzyme-linked immuno-sorbent assay determined serum cytokines. Apoptosis of isolated PMN was delayed significantly in acute coronary syndromes (ACS) as compared with SAP or С (С, 51. 4+/-12. 5 %; SAP, 44. 8+/-13. 4 %, UAP, 28. 3+/-10. 2 %; AMI, 20. 5+/-8. 4 %; AMI or UAP vs. SAP or C, P<0. 001). Moreover, serum of patients with ACS markedly reduced apoptosis of PMN from healthy donors. Analysis of patients' sera revealed significantly elevated concentrations of tumor necrosis factor alpha, interferon-gamma (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin (IL)-l beta in ACS (vs. С and SAP). This study demonstrates a pronounced delay of PMN apoptosis in UAP and AMI, which may result from increased serum levels of IFN-gamma, GM-CSF, and IL-1beta and from enhanced platelet activation Therapeutical modulation of these determinants of PMN lifespan may provide a new concept for the control of inflammation in ACS. These results demonstrate that ischemia/reperfusion injury, apoptotic cell death and immune responses may be exacerbated by cold stress To one of results of our work began revealing steady negative correlation between a level ofinsulinoresistantion, estimated according to value of concentration of glucose in blood, and efficiency of action of trimetazidine, estimated according to a parameter of apoptosis of cardyomyocytes in a cardiac muscle of rabbits in experiment and apoptosis of polymorphonuclear neitrophils in peripheral blood of patients in clinic Direct exposure of whole blood to clinically relevant concentrations of trimetazidine in the absence of infection resulted in modest yet significant delayed of PMN survival (increased apoptosis). The purpose of this study was to determine whether cold-stress stimulation produces continuous hypertension in rabbits. Rabbits were kept in cages with a 0 degrees С floor and 23 degrees С room temperature (cold-stressed group, n = 10) or in cages with 23 degrees С floor and 23 degrees С room temperature (control group, n = 10). BP and levels of plasma catecholamines, serum glucose, and serum insulin were measured, and the histologic characteristics of the kidney and adrenal gland were studied in all groups. After a week of localized cold-stress, BP of the experimental rats were significantly increased over those of the control rats. Significant increases were also seen in plasma epinephrine and norepinephrine, as well as serum insulin concentrations in the rabbits that underwent localized cold stimulation; these changes were not observed in the control rabbits.