Artificial surface-induced inflammation relies on complement factor 5: proof from a deficient person

Area of Science:

• Biomedical Engineering
• Immunology
• Materials Science

Background:

• Artificial surfaces trigger inflammatory responses in blood, involving complement activation and cytokine release.
• Understanding the specific roles of complement components in this process is crucial for developing biocompatible materials.

Purpose of the Study:

• To investigate the complement-dependent and independent inflammatory responses of human whole blood to artificial surfaces.
• To specifically examine the role of complement factor 5 (C5) in artificial surface-induced inflammation using C5-deficient blood.

Main Methods:

• Human whole blood from a C5-deficient patient, reconstituted blood, and control blood were circulated in polyvinyl chloride (PVC) tubing.
• Complement activation was inhibited using compstatin (C3 inhibitor) and a C5a receptor antagonist.
• Leukocyte CD11b expression, granule enzyme release, and 27 cytokines were measured post-incubation.

Main Results:

• C5-deficient blood showed no terminal complement complex formation, unlike reconstituted or control blood.
• Granule enzyme release was partly C3-dependent and partly C5a-dependent.
• Chemokines (IL-8, MCP-1) were C5a-mediated, while growth factors were partly complement-dependent. Interferon-γ increased independently of complement.

Conclusions:

• The polyvinyl chloride surface induces a significant inflammatory response.
• This inflammatory response is largely dependent on complement factor 5 (C5).
• C5a plays a critical role in leukocyte activation and inflammatory mediator release upon surface exposure.