B33-09 Developmental Endothelial Locus-1 (DEL-1), an Endogenous Inhibitor of Neutrophil Extravasation, Is Increased in the Bronchial Epithelium of COPD Patients

Rationale Chronic pulmonary diseases, such as asthma and COPD, are driven by the accumulation of inflammatory cells in the lungs. Developmental Endothelial Locus-1 (DEL-1) is an endogenously secreted protein which abrogates neutrophil migration to inflamed tissues through inhibition of neutrophil adhesion on endothelial cells (1). Prior research shows that DEL-1 levels decrease during active inflammation (2). While one study with a limited sample number showed decreased bronchial epithelial DEL-1 expression in asthma (3), the airway DEL-1 expression in lung tissue of patients with asthma and COPD and its link with disease severity has not been fully elucidated yet. We aimed to measure bronchial epithelial DEL-1 expression in human lung tissue, leveraging our lung tissue biobank from patients with or without asthma or COPD. Methods Paraffin-embedded human lung tissue samples were obtained from patients undergoing tumor resection at Ghent University Hospital (macroscopically normal, n = 100) or from COPD GOLD IV explanted transplant lungs at KU Leuven (n = 10). Patients were defined as having asthma based on a recorded history of asthma. COPD patients were defined based on spirometry data (FEV1/FVC < 70%), with severity graded according to GOLD criteria. Microsections were stained with rabbit anti-human DEL-1 (Proteintech). 1141 total airways were analyzed. DEL-1 staining intensity in the airway epithelium was normalized to epithelial area (Airway Normalized Staining / µm²). The per-patient median of multiple airway values (Bronchial Epithelial DEL-1 Median Normalized Staining / µm²) was used to compare patient groups. Results Compared to controls, bronchial epithelial DEL-1 expression was increased in COPD, but not in asthma or in asthma + COPD (Figure 1A). In patients without COPD and in COPD GOLD I-II, DEL-1 expression showed no differences between current and ex-smokers (Figure 1B). Within COPD, bronchial epithelial DEL-1 expression was not significantly associated with COPD severity, although the highest DEL-1 expression was observed in COPD GOLD III-IV ex-smokers. Conclusion We found that bronchial epithelial DEL-1 expression is increased in COPD patients and - in contrast to prior literature - is similar between asthma and controls. Future analyses will assess associations between DEL-1 expression, airway inflammatory cell counts, and mucus production. References 1) Choi, et al. Science 2008. 322:1101-1104. 2) Tao, et al. J Adv Res 2025. Online ahead of print. 3) Jia, et al. Allergy 2024. 79:1180-1194.