{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T10:05:25Z","timestamp":1779444325761,"version":"3.53.1"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Efferocytosis\u2014the tightly regulated clearance of apoptotic cells by phagocytes\u2014maintains tissue homeostasis and is impaired in chronic obstructive pulmonary disease (COPD), where it contributes to persistent inflammation and increases the risk of comorbidities, including lung cancer. Inhaled corticosteroids (ICS) and long-acting \u03b22 agonists (LABAs) are cornerstones of COPD therapy, but their effects on efferocytosis and on the COPD\u2013lung cancer interface are incompletely understood. The primary objective of this study was to determine whether the ICS fluticasone propionate and the LABA salmeterol xinafoate, alone or in combination at clinically informed concentrations (10\u22128\u201310\u22126 M; 10\u22124 M reserved for cytotoxicity screening), modulate efferocytic capacity and inflammatory cell survival across diverse phagocyte models. We performed standardized in vitro efferocytosis assays using murine peritoneal and alveolar macrophages, the murine macrophage line J774A.1, PMA-differentiated human THP-1 macrophages, human blood-derived neutrophils, and the human alveolar adenocarcinoma cell line A549. Apoptosis was induced in Jurkat T cells by UV irradiation (100 mJ\/cm2) and in murine thymocytes by dexamethasone (1 \u00b5M, 4 h); apoptotic and necrotic populations were characterized by annexin-V\/propidium iodide and Sytox Green\/Hoechst H-33342 staining. Peritoneal macrophages showed the highest efferocytic activity (~75%), followed by J774A.1 (~75% at 24 h), THP-1 (~30% at 2 h; ~60% at 24 h), alveolar macrophages (~40%), and A549 cells (&lt;20%). Neither fluticasone nor salmeterol, individually or in combination, significantly altered efferocytic capacity in any phagocyte tested (all ANOVA p &gt; 0.26). Fluticasone (10\u22128 and 10\u22126 M) significantly improved 24 h neutrophil survival and reduced early apoptosis (p &lt; 0.05) but did not translate this survival benefit into enhanced efferocytosis. Salmeterol was cytotoxic at 10\u22124 M and inactive at 10\u22128\u201310\u22126 M. These findings indicate that the established anti-inflammatory benefits of ICS\/LABA in COPD do not extend to augmentation of efferocytosis in this acute, serum-free in vitro setting and that pharmacological restoration of efferocytosis in COPD\u2014a defect implicated in the pathogenesis and progression of comorbid lung cancer\u2014will likely require strategies targeting the efferocytic machinery itself (e.g., MerTK, Rac-1, MFG-E8) rather than relying on current inhaled therapy.<\/jats:p>","DOI":"10.3390\/ijms27104627","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:06:07Z","timestamp":1779365167000},"page":"4627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Inhaled Corticosteroids and Long-Acting \u03b22-Agonists on Efferocytosis and Inflammatory Cell Survival: An In Vitro Study Relevant to COPD and Lung Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Bassam","family":"Redwan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Knappschaft Kliniken Gelsenkirchen Buer, Schernerweg 4, 45894 Gelsenkirchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Biancosino","sequence":"additional","affiliation":[{"name":"Helios University Hospital Wuppertal, University of Witten\/Herdecke, 42283 Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Lung Assist, Klinikum Ibbenb\u00fcren, 49477 Ibbenb\u00fcren, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-5258","authenticated-orcid":false,"given":"Sabina","family":"Janciauskiene","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hannover Medical School (MHH), Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Golpon","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hannover Medical School (MHH), Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.it.2015.11.008","article-title":"Neutrophils in the tumor microenvironment","volume":"37","author":"Powell","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1046\/j.1440-1711.2003.t01-1-01170.x","article-title":"Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells","volume":"81","author":"Hodge","year":"2003","journal-title":"Immunol. 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