Plasma factor triggering alternative complement pathway activation by liposomes

Area of Science:

• Biochemistry
• Immunology
• Nanotechnology

Background:

• Plasma components, including complement (C) proteins, are crucial for clearing liposomes from circulation.
• Liposome-membrane interactions with the C system affect liposome stability and clearance rates.

Purpose of the Study:

• To investigate the interactions between liposomes and the complement system.
• To understand how mannose density on liposomes influences complement activation and clearance.

Main Methods:

• Utilized multilamellar vesicle (MLV) liposomes with varying densities of cetylmannoside (Man).
• Assessed complement activation through the alternative pathway for both Man-modified (Man-MLV) and unmodified (PC-MLV) liposomes.
• Investigated the effect of plasma preadsorption on Man-MLV and PC-MLV-induced complement activation.

Main Results:

• Complement activation damaged MLV liposomes, with susceptibility dependent on mannose density.
• Mannose-modified liposomes activated the alternative C pathway, similar to unmodified liposomes.
• Preadsorption of plasma with Man-MLV abolished its capacity to activate the alternative C pathway, unlike with PC-MLV.
• A specific plasma factor adsorbed by Man-MLV was identified as responsible for augmenting C activation.

Conclusions:

• Mannose density on liposomes modulates complement activation via the alternative pathway.
• Rapid clearance of Man-MLV is attributed to enhanced C-mediated liposome permeability and phagocytosis.
• A specific plasma factor interacting with mannose moieties enhances complement activation and liposome clearance.