Abstract Diesel exhaust particles (DEP) remain a major contributor to ambient PM2.5 in many regions and are implicated in air pollution-mediated pulmonary vascular disease. We investigated whether alveolar DEP exposure triggers oxidative and inflammatory responses and generates soluble mediators capable of acting on human pulmonary arterial endothelial cells (HPAECs), thus inducing inflammation, vascular damage and dysfunction. A human quasi–air–liquid interface alveolar model composed of primary microvascular endothelial cells, alveolar epithelial cells, fibroblasts and THP-1 macrophages was repeatedly exposed to non-cytotoxic doses of standard DEP (SRM2975) for 96 h. Conditioned medium from exposed cultures was applied to primary HPAECs. In the alveolar model, DEP caused a concentration-dependent increase of the oxidative stress markers NRF2, NQO1 and mitochondrial SOD2, but not the predominantly cytosolic SOD1, aligning with elevated mitochondrial biogenesis markers (NRF1, TOMM20, NDUFB8). Gene expression of the proinflammatory cytokines IL1B, IL8, and TNFA, as well as secretion of IL-8 was increased in a concentration- and time-dependent manner. In HPAECs, preliminary data suggested that conditioned medium from DEP-exposed alveolar cultures similarly increased cell-surface adhesion molecule VCAM-1. Similarly, recombinant TNFα augmented VCAM-1 and ICAM-1, triggered secretion of the tissue remodelling factor TGF-b1, and reduced intracellular levels of BMPR2, a receptor protective against pulmonary vascular remodelling. DEP therefore provoke alveolar oxidative stress and inflammatory signalling that generate mediators capable of indirectly driving endothelial dysfunction in the pulmonary arterial endothelium. Further experiments on this indirect effect in a human pulmonary artery-on-a-chip in vitro model and mice will help understand its impact on pulmonary circulation.
Bredeck et al. (2026) studied this question.