Enhanced hydroxyl radical generation by human leukocytes exposed to bacterial diamines highlighting immunomodulatory effect of microbial metabolites

Recently, there have been increasing an interest to study a role of polyamines in intercellular interactions, especially in the focus of inflammation, where accumulation of such polycations is observed. In this regard, products of microbial origin — cadaverine and putrescine — are of particular attention. The role of polyamines as «scavengers» of free radicals has been described, but no data of their effect on the leukocyte radical-producing activity have been obtained so far. The aim of the investigation was to study features of hydroxyl radical generation by human leukocytes exposed to microbe-derived polyamines. Materials and methods. Peripheral venous blood samples were obtained from 20 healthy donors. To assess radical production, a luminol-dependent chemiluminescence reaction was carried out with blood leukocytes pre-incubated with cadaverine (0.01 M) and putrescine (0.01 M), measured on a Luminoskan Ascent^® Thermo Labsystems luminometer (USA) for 180 min. For statistical analysis, an integral chemiluminescence index was used for the entire measurement period (RLU). Results and discussion. It was shown that cadaverine has a stimulating effect on the leukocyte potential to produce radicals (averaged area under the curve is 6.7±0.7 r.u., p < 0.05). Putrescine had little effect on the radical-producing activity of human cells (2.8±0.4 r.u., p < 0.05). This might be due to the direct influence of polycations on the mechanisms of radical generation, as well as increased activity of leukocyte diamine oxidase catalyzing the conversion of diamines into aminoaldehyde, which is accompanied by the release of hydrogen peroxide reacting with luminol. In addition, the enzyme inactivates other compounds, such as histamine leading to formation of a less pronounced clinical picture. Polyamines, particularly cadaverine and putrescine, can be referred to the factors remodeling the metabolic activity of the host leukocytes, which is aimed at maintaining the viability and increasing the number of microorganisms. Conclusion. Thus, cadaverine and putrescine produced by microorganisms, depending on the conditions of the microenvironment, might be evidently considered as mediators of the mild or asymptomatic course of inflammatory diseases, which contributes to underlying persistent potential of bacteria.