Transriptome Analysis of Peripheral Blood Monocytes in Chronic Obstructive Pulmonary Disease Patients.

Abstract

: The aim of the study was to perform monocyte transcriptome analysis for identification of differentially expressed genes and key disturbances in biological processes in these cells in COPD. . The study included three COPD patients and three smokers without bronchial obstruction. Monocytes were obtained from peripheral blood mononuclear cells using the plastic adhesion method. The cell purity achieved as a result of enrichment was approximately 90% according to flow cytometry data. The isolated RNA samples were purified from genomic DNA and ribosomal RNA. The samples were sequenced on a MGISEQ-200 sequencer in SE50 mode. Read mapping and transcript counting were performed in Salmon v1.10.1 software; further data processing was carried out in R software environment. : As a result of the analysis, 21 upregulated and 29 downregulated genes were found in monocytes from COPD patients. Among the genes with increased expression, the most significant were the noncoding RNAs PKD1P5-LOC105376752 and PKD1P4-NPIPA8, the role of which remains unclear, as well as SETDB2, RNASE6, SERPINE1, and MRC1. Downregulated genes, of which F8A2, ZDHHC19, CXCL9, CXCL10, HBA1, HBB, C2, CFB, CFD, MT1B, MT1G, and TIMP3 were of most interest, showed enrichment in seven gene ontology (GO) terms, including those related to response to lipopolysaccharides, hydrogen peroxide, copper ions, and complement activation. . The data obtained indicate inhibition of monocyte functional activity in COPD patients with a decrease in the ability to provide effective protection against microbial pathogens while weakening self-protection against reactive oxygen species. Upregulation of SERPINE1 and downregulation of TIMP3 may significantly contribute to airway remodeling and emphysema development in COPD.