@article {Fujii00915-2020, author = {Wataru Fujii and Theodore S. Kapellos and Kevin Ba{\ss}ler and Kristian H{\"a}ndler and Lisa Holsten and Rainer Knoll and Stefanie Warnat-Herresthal and Marie Oestreich and Emily R. Hinkley and Jan Hasenauer and Carmen Pizarro and Christoph Thiele and Anna C. Aschenbrenner and Thomas Ulas and Dirk Skowasch and Joachim L. Schultze}, title = {Alveolar macrophage transcriptomic profiling in COPD shows major lipid metabolism changes}, elocation-id = {00915-2020}, year = {2021}, doi = {10.1183/23120541.00915-2020}, publisher = {European Respiratory Society}, abstract = {Background Immune cells play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Albeit established changes in distribution and cellular functions of major immune cells, such as alveolar macrophages (AMs) and neutrophils, their transcriptional reprogramming and contribution to the pathophysiology of COPD are still not fully understood.Aim and methods To determine changes in transcriptional reprogramming and lipid metabolism in the major immune cell type within the bronchoalveolar lavage fluid, we analysed whole transcriptomes and lipidomes of sorted CD45+Lin-HLA-DR+CD66b-Autofluorescencehi AMs from control and COPD patients.Results We observed global transcriptional reprogramming featuring a spectrum of activation states, including pro- and anti-inflammatory signatures. We further detected significant changes between COPD patients and controls in genes involved in lipid metabolism, such as fatty acid biosynthesis in GOLD2 patients. Based on these findings, assessment of a total of 202 lipid species in sorted AMs revealed changes of cholesteryl esters, monoacylglycerols and phospholipids in a disease grade-dependent manner.Conclusions Transcriptome and lipidome profiling of COPD AMs revealed GOLD grade-dependent changes, such as in cholesterol metabolism and interferon alpha and gamma responses.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: All authors have no conflict of interest to disclose.}, URL = {https://openres.ersjournals.com/content/early/2021/04/29/23120541.00915-2020}, eprint = {https://openres.ersjournals.com/content/early/2021/04/29/23120541.00915-2020.full.pdf}, journal = {ERJ Open Research} }