[Dynamic analysis of modification of peripheral neutrophils functional activity and its regulation during tumor...

Polymorphonuclear granulocytes (neutrophils) release the reactive oxygen species (ROS) for destruction of pathogens, providing quicker of an organism from infections and own defective of transformed cells. Reactive oxygen species are also potential carcinogens because they facilitate mutagenesis, tumor promotion and progression. Balance between these opposite influences is supported by coordinated interrelations in intracellular signaling systems. Tumor growth influence on the NADPH oxidase in peripheral innate immune cells is unclear. A solid cancer model was developed after an intramuscular injection of Ehrlich carcinoma cells into hind leg of NMRI strain mice. Intensity of the respiratory burst was estimated by luminol-dependent chemiluminescence technique. Transformation of inflammatory reaction was revealed during tumor growth: greater amounts of neutrophils were recruited into peritoneal cavity; sizes of the cells, their nuclei and granules were enlarged; the ratio of different cell types in peritoneal exudation was changed. The study revealed that tumor progression was accompanied by significant changes in functional activity of neutrophils. Dynamic increase in spontaneous level of ROS production and concentration-dependent change of intensity of the respiratory burst induced with chemotactic peptide N-formyl-Met-Leu-Phe (fMLF) was revealed in peripheral neutrophils under tumor growth conditions. It was found that effects of inhibitors of tyrosine protein kinases, protein kinase C, mitogen-activated protein kinase p38MAPK (p38MAPK) and phosphatidylinositol 3-kinase (PI3K) were altered in neutrophils from tumor-bearing mice in comparison with the cells of control mice. This indicates a change in the role of the enzymes in regulation of the neutrophil respiratory burst. Data obtained show that p38MAPK and PI3K entangle up- and down-regulation of NADPH oxidase in peripheral neutrophils during tumor growth.