Efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS

Area of Science:

• Pulmonary immunology
• Lymphatic physiology
• Sepsis research

Background:

• The lymphatic system is crucial for resolving inflammation.
• Pulmonary lymphatic drainage in sepsis-induced acute respiratory distress syndrome (ARDS) is not well understood.
• Sepsis significantly impacts lymphatic function and inflammatory responses.

Purpose of the Study:

• To investigate the role of pulmonary lymphatic drainage in sepsis-induced ARDS.
• To explore the therapeutic potential of vascular endothelial growth factor-C (VEGF-C) in restoring lymphatic function during ARDS.
• To elucidate the mechanisms underlying lymphatic dysfunction in sepsis.

Main Methods:

• Utilized indocyanine green-near infrared lymphatic living imaging in septic mouse models.
• Examined pulmonary lymphatic drainage function and lymphatic structure.
• Investigated the effects of blocking vascular endothelial growth factor receptor-3 (VEGFR-3) and administering VEGF-C156S.
• Assessed the levels of CC chemokine ligand 21 (CCL21) and inflammatory cell infiltration.

Main Results:

• Sepsis-induced ARDS impairs pulmonary lymphatic drainage due to structural damage.
• Blocking VEGFR-3 exacerbated lymphatic dysfunction and inflammation.
• Post-treatment with VEGF-C156S rejuvenated lymphatics, reduced pulmonary edema, and promoted the drainage of macrophages and neutrophils.
• VEGF-C156S treatment reversed sepsis-induced inhibition of CCL21, crucial for lymphatic function.
• The therapeutic benefits of VEGF-C156S were dependent on VEGFR-3 and CCL21 signaling.

Conclusions:

• Efficient pulmonary lymphatic drainage is essential for resolving inflammation in ARDS.
• VEGF-C156S therapy shows promise in ameliorating sepsis-induced ARDS by enhancing lymphatic drainage.
• Targeting lymphatic function represents a novel therapeutic avenue for ARDS management.