Blood platelet and monocyte activations and relation to stages of liver cirrhosis

AIM: Blood platelets (pIt) and monocytes are the cells that play a crucial role in the pathogenesis of liver damage and liver cirrhosis (LC). In this paper, the analysis of mutual relationship between platelets and monocytes activation in LC was conducted. METHODS: Immunofluorescent flow cytometry was used to measure the percentage of activated platelet populations (CD62P, CD63), the percentage of plt-monocyte aggregates (pma) (CD41/CD45), and activated monocytes (CD11b, CD14, CD16) in the blood of 20 volunteers and 40 patients with LC. Platelet activation markers: sP-selectin, platelet factor 4 (PF4), beta-thromboglobulin (PTG) and monocyte chemotactic peptide-1 (MCP-1) were measured and compared in different stages of LC. RESULTS: Platelet activation with the increase in both βTG serum concentration and elevation of pIt population (CD62P and CD63 as well as MIF CD62P and CD63) is elevated as LC develops and thrombocytopenia rises. There is a positive correlation between medial intensity of fluorescence (MIF) CD62P and MIF CD63 in LC. We did not show any relationship between monocyte activation and pma level. SP-selectin concentration correlates positively with pIt count and pma, and negatively with stage of pIt activation and MIF CD62P and MIF CD63. There was no correlation between MCP-1 concentration and pIt, monocyte activation as well as pma level in LC. CD16 monocytes and MIF CD16 populations are significantly higher in the end stage of LC. A positive correlation occurs between the value of CDllb monocyte population and MIF CD14 and MIF CD16 on monocytes in LC. CONCLUSION: Platelet and monocyte activation plays an important role in LC. Platelet activation stage does not influence monocyte activation and production of pIt aggregates with monocytes in LC. With LC development, thrombocytopenia may be the result of pIt consumption in platelet-monocyte aggregates.

Phagocytic and oxidative burst activity of neutrophils in the end stage of liver cirrhosis

AIM：To evaluate the phagocytic activity and neutrophil oxidative burst in liver cirrhosis.METHODS： In 45 patients with advanced postalcoholic liver cirrhosis （aged 45±14 years） and in 25 healthy volunteers （aged 38±5 years）, the percentage of phagocytizing cells after in vitro incubation with E. coli （Phagotest Kit）, phagocytic activity （mean intensity of fluorescence, MIF） and the percentage of neutrophil oxidative burst （Bursttest Kit）, and the level of free oxygen radical production （MIF of Rodamine 123） were analyzed by flow cytometry. The levels of soluble sICAM-1, sVCAM-1, sP-selectin, sE-selectin, sL-selectin, and TNF-α were determined in blood serum.RESISTS： The percentage of E. coli phagocytizing neutrophils in liver cirrhosis patients was comparable to that in healthy subjects. MIF of neutrophil - ingested E. coli was higher in patients with liver cirrhosis. The oxidative burst in E. coli phagocytizing neutrophils generated less amount of active oxygen compounds in liver cirrhosis pa- tients （MIF of R123：24.7±7.1 and 29.7±6.6 in healthy, P〈0.01）. Phorbol myristate acetate （PMA） - stimulated neutrophilsproduced less reactive oxidants in liver cirrhosis patients than in healthy subjects （MIF of R123： 42.7±14.6 vs 50.2±13.3, P〈0.01）. A negative correlation was observed between oxidative burst MIF of PMA-stimulated neutrophils and ALT and AST levels （r -0.35, P〈0.05; r-0.4, P〈0.03）. sVCAM-1, sICAM-1, sE-selectin concentrations correlated negatively with the oxygen free radical production （MIF of R123） in neutrophils after PMA stimulation in liver cirrhosis patients （r-0.45, P〈0.05, r-0.41, P〈0.05; r-0.39, P〈0.05, respectively）.CONCLUSION： Neutrophil metabolic activity diminishes together with the intensification of liver failure. The metabolic potential of phagocytizing neutrophils is significantly lower in liver cirrhosis patients, which can be one of the causes of immune mechanism damage. The evaluation of oxygen metabolism of E. coli-stimulated neutrophils reveals that the amount of released oxygen metabolites is smaller in liver cirrhosis patients than in healthy subjects.