Carbon monoxide alleviates endotoxin-induced acute lung injury via NADPH oxidase inhibition in macrophages and neutrophils.
Summary
In endotoxin ALI models, CO—delivered via hemoglobin vesicles—attenuated lung injury by inhibiting NOX in neutrophils and macrophages, suppressing ROS, TLR4/NF-κB signaling, and M1-like polarization. These data position NOX and redox signaling as actionable targets in sepsis-related ALI/ARDS.
Key Findings
- CO inhibited NOX activity in neutrophils and macrophages, reducing ROS and TLR4/NF-κB signaling.
- CO-HbV therapy mitigated LPS-induced ALI, decreasing oxidative/inflammatory responses and neutrophil/M1-like macrophage infiltration in BALF.
- Macrophage polarization toward an M1-like phenotype was suppressed by CO across cellular systems.
Clinical Implications
Suggests exploring NOX inhibition and CO-donor strategies as adjunctive therapies in early sepsis-related ALI/ARDS, with careful safety evaluation and dosing.
Why It Matters
Provides a mechanistic, targetable pathway (NOX–TLR4–NF-κB) and a drug delivery modality (CO-HbV) with translational potential for sepsis-related ALI/ARDS.
Limitations
- Preclinical models; clinical translatability and safety of CO delivery remain unproven
- Sample sizes and long-term outcomes were not detailed in the abstract
Future Directions
Define dose–exposure–response and safety windows for CO-HbV, validate in large-animal sepsis/ALI, and develop biomarkers of NOX/TLR pathway engagement for early-phase trials.
Study Information
- Study Type
- Case-control
- Research Domain
- Treatment
- Evidence Level
- V - Preclinical experimental work in animal and cell models comparing treatment vs control
- Study Design
- OTHER