Interactions of C-reactive protein and complement with liposomes

Area of Science:

• Immunology
• Biochemistry
• Materials Science

Background:

• C-reactive protein (CRP) is a key acute-phase protein involved in innate immunity.
• Liposomes are versatile model systems for studying membrane interactions.
• The complement system is a critical component of the immune system.

Purpose of the Study:

• To investigate the interactions between C-reactive protein (CRP) and liposomal model membranes.
• To elucidate the role of the complement pathway in CRP-mediated liposome damage.
• To determine the optimal liposome composition for CRP-initiated complement activation.

Main Methods:

• Investigated CRP interactions with liposomes containing phosphatidylcholine in human serum.
• Assessed complement component consumption (C1-C9) and glucose release from liposomes.
• Utilized liposomes with varying lipid compositions, charges, and glycolipids.
• Employed C2-deficient human serum and guinea pig complement for mechanistic studies.

Main Results:

• CRP initiated complement-dependent damage and glucose release from specific liposomes.
• Optimal liposome damage occurred with positively charged liposomes containing phosphatidylcholine and galactosylceramide.
• Glucose release was inhibited by phosphocholine and dependent on C2 and C1q.
• Background lysis, independent of CRP, involved terminal complement components.

Conclusions:

• CRP sensitizes specific liposomes to complement-dependent damage via the classical pathway starting at C1q.
• Liposomes containing phosphatidylcholine, positive charge, and ceramide glycolipids are most susceptible to CRP-mediated damage.
• These liposomes also exhibit CRP-independent complement lysis, primarily involving terminal components.