Lysophospholipids are formed as a result of hydrolysis of glycerophospholipids localized in biological membranes and lipoproteins catalyzed by phospholipases A2 (PLA2) [1]. The products of PLA2 functioning regulate the processes of signal transduction in response to external stimuli. PLA2 plays an important role in the development of pathological conditions associated with oxidative stress formation caused by reactive oxygen species (ROS) hyperproduction. It has been previously shown that ROS induce lysophospholipids destruction. The interaction of lysophosphatidylcholine with ROS is accompanied by lipid molecule fragmentation with the formation of predominantly palmitoxyacetone and stearoxyacetone. The formation of such products from lysophospholipids is possible only through the free radical pathway since the enzymatic systems leading to the accumulation of these compounds have not been found in the human body.
ROS are produced mainly by neutrophils as a result of the enzymes NADPH oxidase and myeloperoxidase activation, which generate superoxide radical anions and hypochlorous acid, respectively [2]. Palmitoxyacetone, formed in the inflammatory focus as a result of ROS-induced free radical fragmentation of lysophospholipids, can change the functional activity of neutrophils, and thus regulate the inflammatory process, which makes this work relevant.
Neutrophils were isolated from the peripheral blood of healthy people in a Histopaque-1077 density gradient according to a standard technique. Cell survival was studied using propidium iodide (${\lambda}ex = 530$ nm, ${\lambda}em = 640$ nm). ROS generation by neutrophils was determined by the fluorescent method using the H2DCF-DA probe (${\lambda}ex = 488$ nm, ${\lambda}em = 530$ nm). The cells were stimulated to phagocytosis with the chemotactic peptide fMLP. The measurements were carried out at T = 37 °C, pH = 7.2.
It has been shown that palmitoxyacetone in the concentration range of $0.1{\text{--}}100$ μM doesn't have a toxic effect on cells. It was found that cells incubation with palmitoxyacetone at a concentration of $100$ μM for 30 min leads to a decrease, and at a concentration of 1 and $10$ μM, to an increase in H2O2 production by fMLP-stimulated neutrophils, while $0.1$ μM palmitoxyacetone does not affect this process.
Thus, palmitoxyacetone can regulate ROS generation by neutrophils.