Complement depletion enhances pulmonary inflammatory response after liver injury

Area of Science:

• Immunology
• Hepatology
• Pulmonology

Background:

• Hepatic cryoablation can lead to acute lung injury.
• This injury involves nuclear factor (NF)-kappaB activation, chemokine production, and neutrophil infiltration in the lungs.
• The complement system and Kupffer cells play a role in this inflammatory response.

Purpose of the Study:

• To investigate the role of the complement system in acute lung injury following hepatic cryoablation.
• To examine the impact of complement depletion on NF-kappaB activation and pulmonary inflammation.

Main Methods:

• HLL transgenic mice, which report NF-kappaB activity via a luciferase gene, were used.
• Total complement was depleted using cobra venom factor (CVF) before cryoablation.
• NF-kappaB activity, chemokine levels, and neutrophil infiltration were measured in the liver and lungs.

Main Results:

• Complement depletion did not alter NF-kappaB activation in the liver remnant post-cryoablation.
• Complement depletion significantly increased NF-kappaB activation in the lungs at early and late time points.
• Chemokine levels and neutrophil influx into the lungs were significantly higher in complement-depleted mice.

Conclusions:

• Complement depletion exacerbates pulmonary inflammation after hepatic cryoablation, primarily through increased NF-kappaB activity.
• Activated complement is not the initiator of the systemic inflammatory response post-cryoablation.
• Downstream components of the complement cascade may play a role in diminishing subsequent inflammation.