Effect of dexamethasone on human neutrophil adhesion and concomitant secretion

Abstract

Neutrophils play a dual role in protecting the body. They are able to penetrate infected tissues and destroy pathogens there, releasing aggressive bactericidal substances. Getting into the surrounding tissues, aggressive secretion products of neutrophils initiate the development of inflammatory processes. Invasion of neutrophils into tissues is observed during the development of pneumonia in patients with lung diseases of various etiologies, including acute respiratory distress syndrome caused by coronavirus disease. The synthetic corticosteroid hormone dexamethasone has a therapeutic effect in the treatment of lung diseases, including reducing mortality in patients with severe Covid-19. The acute (short-term) effect of dexamethasone on neutrophil adhesion to fibrinogen and concomitant secretion was studied. Dexamethasone did not affect either the attachment of neutrophils to the substrate or their morphology. The production of reactive oxygen species (ROS) and nitric oxide (NO) by neutrophils during adhesion also did not change in the presence of dexamethasone. Dexamethasone stimulated the release of metalloproteinases in addition to proteins secreted by neutrophil adhesion under control conditions, and selectively stimulated the release of the free amino acid hydroxylysine, a product of lysyl hydroxylase. Metalloproteinases play a key role and closely interact with lysyl hydroxylase in the processes of rearrangement of the extracellular matrix. The therapeutic effect of dexamethasone may be associated with its ability, by changing the composition of neutrophil secretions, to reorganize the extracellular matrix in tissues, which can lead to improved gas exchange in patients with severe lung diseases.