Inhibition of Neutrophil Secretion Upon Adhesion as a Basis for the Anti-Inflammatory Effect of the Tricyclic Antidepressant ImipramineстатьяИсследовательская статья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 29 сентября 2021 г.
Аннотация:Recent studies demonstrate the involvement of inflammatory processes in thedevelopment of depression and the anti-inflammatory effects of antidepressants.Infiltration and adhesion of neutrophils to nerve tissues and their aggressive secretionare considered as possible causes of inflammatory processes in depression. We studiedthe effect of the antidepressant imipramine on the adhesion and accompanied secretion ofneutrophils under control conditions and in the presence of lipopolysaccharides (LPS). Asa model of integrin-dependent neutrophil infiltration into tissues, we used integrindependentadhesion of neutrophils to the fibronectin-coated substrate. Imipramineinhibited neutrophil adhesion and concomitant secretion of proteins, including matrixmetalloproteinase 9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL), whichmodify the extracellular matrix and basement membranes required for cell migration.Imipramine also significantly and selectively blocked the release of the free amino acidhydroxylysine, a product of lysyl hydroxylase, an enzyme that affects the organization of theextracellular matrix by modifying collagen lysine residues. In contrast, imipramineenhanced the release of ROS by neutrophils during adhesion to fibronectin andstimulated apoptosis. The anti-inflammatory effect of imipramine may be associatedwith the suppression of neutrophil infiltration and their adhesion to nerve tissues byinhibiting the secretion of neutrophils, which provides these processes.