Heme-induced lung injury in human precision cut lung slices: a new model for acute lung injury.
Summary
Circulating heme is elevated in COVID-19 ARDS and induces dose-dependent cell death, inflammatory cytokine release, and ECM remodeling in human precision-cut lung slices. The heme-stimulated PCLS model reproduces inflammatory signatures seen in patient blood, providing a human-relevant ex vivo platform for ARDS research.
Key Findings
- Serum heme and HO-1 levels are elevated in patients with COVID-19 and ARDS versus controls.
- Heme induces dose-dependent cell death, proinflammatory signaling, and extracellular matrix changes in human PCLS.
- Integrative omics identified 27 shared markers (adj p<0.05), aligning with inflammatory cytokines elevated in patient blood; LPS did not augment heme cytotoxicity.
Clinical Implications
Supports investigation of heme-scavenging and heme metabolism-modulating strategies (e.g., hemopexin, HO-1 pathways) as potential interventions in ARDS.
Why It Matters
Introduces a human tissue-based ex vivo model linking circulating heme to ARDS-like injury, addressing a key bottleneck in translational ARDS research.
Limitations
- Ex vivo model lacks systemic immune-vascular interactions and mechanical forces.
- Sample size and etiologic generalizability beyond COVID-19 ARDS are not detailed.
Future Directions
Evaluate heme-scavenging interventions in PCLS and in vivo; test across diverse ARDS etiologies and integrate with biomechanical injury models.
Study Information
- Study Type
- Basic/Mechanistic Research
- Research Domain
- Pathophysiology
- Evidence Level
- V - Ex vivo human tissue model with supportive patient biomarker data; no clinical intervention testing.
- Study Design
- OTHER