Platelet-leukocyte interactions: immunoregulatory role and pathophysiological relevance

Blood platelets are the central players in thrombosis and blood coagulation. Moreover, they also exhibit immunoregulatory properties and bridge hemostasis and immunity. Morphological and functional characteristics of the platelets ensure continuous surveillance for the vascular system, recognition of different hazards, development of appropriate response and recruitment of immune cells. Indirect platelet-leukocyte interactions are mediated by immunoregulatory molecules that are released, along with coagulation and thrombosis factors in the course of platelet activation and degranulation. Chemokines, cytokines, growth factors, some of which are synthesized de novo, are released from activated platelets and modulate cellular functions, thus modulating both innate and adaptive immune response. Activated platelets enter contacts with immune cells to form heterotypic aggregates, i.e., platelet-leukocyte complexes that reside in blood circulation along with other blood cells. The aggregate formation and stabilization is mediated by interaction between the molecules expressed on the surface of platelets and leukocytes, in particular, P-selectin (CD62P) and PSGL-1 (CD162). Platelet-monocyte and platelet-neutrophil complexes are most abundant, with platelet-monocyte aggregates being most stable. Moreover, the platelet-derived microvesicles also interact with leukocytes to form heterotypic aggregates, thus, probably, modulating the immune cell functions via transfer of non-coding RNA molecules. Formation of platelet-leukocyte complexes results into mutual activation of platelets and leukocytes. Platelets and platelet-derived microvesicles stimulate phagocytic activity, cytokine secretion, and generation of reactive oxygen species in monocytes and neutrophils, inducing formation of neutrophilic extracellular traps and procoagulant phenotype in monocytes. The blood platelets regulate monocyte differentiation, promote adhesion, as well as transmigration of lymphocytes and NK cells. At the sites of inflammation, platelets enhance extravasation and infiltration of leukocytes into the damaged tissue. Impaired interactions of platelets with endothelial layer and immune cells may underlie pathogenic conditions. Increased level of circulating plateletleukocyte complexes is observed in various disorders including cardiovascular diseases, acute ischemic stroke, respiratory disorders, renal pathologies, liver diseases, diabetes, reproductive disorders, bacterial and viral infections. Further studies of platelet-leukocyte interactions are warranted to unveil pathogenic mechanisms and to develop new therapeutic approaches

Flow cytofluorimetric detection and immunophenotyping of platelet-monocyte complexes in peripheral blood

Activated platelets aggregate with monocytes by binding membrane bound molecules. Platelet-monocyte interaction is considered to underlie pathophysiological mechanisms bridging thrombosis and inflammation. Detection and analysis of platelet-monocyte complexes (PMC) provide means for revealing their physiological and pathogenetic roles and are instrumental in the diagnostics of various pathological conditions including obstetric complications. The aim of the study was to develop the method of quantitative determination of peripheral blood PMC, that preserve phenotypic features of platelets and monocytes, and to reveal their changes by ex vivo analysis. The suggested procedure includes immediate fixation of blood sample, immunocytochemical staining with fluorochrome-conjugated specific antibodies against markers of activation and differentiation followed by lysis of erythrocytes, and flow cytometric analysis. Fourteen samples of peripheral blood from patients with history of pregnancy complication were obtained in first trimester of ongoing pregnancy and analyzed. It was demonstrated that quantitative and qualitative in vivo characteristics of PMC remained unchanged in fixed samples, whereas the number of PMC and expression levels of the markers of platelet and monocyte activation dramatically increased in the unfixed blood. The set of monoclonal antibodies and gating strategies, used in this study, ensure phenotyping and evaluation of percentage/absolute count of PMC in the total monocyte population (CD45+CD14+) and in the subpopulations of classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14lowCD16+) monocytes. This approach provides insight into the participation of different monocyte subsets in the formation of PMC and their roles in physiological and pathophysiological processes. In some samples, elevated PMC proportion was observed, accompanied by significant increase in the expression of platelet activation marker CD62P and decrease in the expression of its monocytic ligand CD162. These changes suggested altered activation of PMC and their participation in the pathophysiological mechanisms of some pregnancy complications. Immunophenotyping of PMC affords an opportunity to characterize their proinflammatory, procoagulant and adhesive properties; these results can be used for research and diagnostics. In particular, the method is suitable for detection and phenotyping of PMC in pregnancy complications and other pathological conditions associated with the disorders of hemostasis and thrombosis

EXPLOITATION RELIABILITY OF RECUPERATORS

The investigations and experience of implementation of constructions, that provide increase of gas-tightness of heat-exchangers, are described in the article. The given variants of compensators of different types allow to increase the reliability of operation of systems of the fuel furnaces waste flue gases heat using

PATTERNS OF REGULATORY T-CELLS AND NK-CELLS LEVELS IN PATIENTS WITH HEPATITIS C VIRUS INFECTION

Abstract. The clinical course of hepatitis C virus infection partially depends on the patient’s immune system status. It was shown that balance between levels of regulatory T-cells and activated NK-cells changed depending on viral load and virus genotype. Patients with high viral load demonstrated shift of this balance toward regulatory T-cells increasing

HEATING SETTINGS OF THE BURDEN HEATING FOR ELECTRO-MELTING

The work of the burden heating outfits for electrosmelting is considered. It is shown that equipping of heating units by the system KIP allows to receive considerable economic and ecological effect

Correction of Psychoemotional State in Pregnant Women with Diffuse Toxic Goiter According to Minnesota Multiphasic Personality Inventory

Using Minnesota Multiphasic Personality Inventory, we have examined 50 pregnant women with diffuse toxic goiter of first and the second stage in the second trimester of pregnancy, before and after combined therapy. Studies show changes in psychoemotional state, psychological maladjustment, which require timely diagnosis and is effectively corrected by means of therapeutic regimen using glutargin and citoflavin

Cupola plant with the low-energy-intensive system of flue gas purification

In the article there is given the description of the realized at Gomel enterprise '^SANTEP'' project of 3 ton cupola with the system of low-energy gas cleaning. The offered system at a low production cost provides efficient cleaning of gas emissions from dust and detrimental impurities

DIAGNOSTIC VALUE OF IMMUNOLOGICAL EXAMINATION IN SPECIFYING A ROLE OF HERPESVIRUS INFECTION IN DEVELOPMENT OF HEMORRHAGIC VASCULITIS WITH RENAL IMPAIRMENT

Determination of etiologic and\or trigger role of herpesvirus infection, immune disorders in development of hemorrhagic vasculitis with renal impairment is useful for optimizing treatment of such patients. Detection of herpes virus activation markers and disorders of immune status in the development of hemorrhagic vasculitis with renal impairment substantiates complex therapeutic schedules including antiviral and immunocorrection drugs. A timely and purposeful antiviral therapy promotes earlier fading of clinical signs typical to hemorrhagic vasculitis. A long-lasting activation of humoral immune system in combination with urinary syndrome suggests a higher risk of immune nephropathy progression, thus requiring long-termmonitoring and implementation of appropriate therapy