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Elevated neutrophil elastase and acrolein-protein adducts are associated with W256 regression

The involvement of granulocytes in immune response against cancer is not well understood. Depending on the cytokine milieu in which they act and on their oxidative burst, granulocytes may play either an inhibitory or stimulatory role in tumor growth. Unsaturated fatty acids, essential components of cellular membranes and storage lipids, are susceptible to granulocyte derived reactive oxygen species (ROS). ROS can induce lipid peroxidation (LPO) resulting in the destruction of biomembranes. Thus, murine W256 tumor progressing and tumor regressing animal models were used to study the involvement of plasma inflammatory mediators and oxidative burst of circulating granulocytes in malignant destruction and detrimental tumor growth. The involvement of LPO-derived aldehydes (i.e. acrolein, 4-hydroxy-2-nonenal and malondialdehyde) and myeloperoxidase (MPO) appearance in granulocyte anticancer response were further evaluated. The results obtained revealed a significant increase in neutrophil elastase in animals with regressing tumor. Furthermore, the presence of MPO in tumor microenvironment was accompanied by the formation of acrolein only five hours after tumor transplantation and its presence increased during tumor regression. Latter in an early stage of tumor regression, the presence other LPO-derived aldehydes were also observed. The obtained results suggest that elevated neutrophil elastase and initiation of LPO may play an important role in the tumor development leading to tumor regression.

granulocytes; interleukin 17; lipid peroxidation; neutrophil elastase; tumor regression

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