Liposome-induced activation of the classical complement pathway does not require immunoglobulin

Area of Science:

• Immunology
• Biochemistry
• Liposome research

Background:

• Liposomes are frequently utilized in biomedical applications, including drug delivery systems.
• Complement activation by liposomes can lead to immune responses, influencing their efficacy and safety.
• The role of immunoglobulins in liposome-mediated complement activation remains incompletely understood.

Purpose of the Study:

• To investigate the contribution of immunoglobulins to complement activation induced by liposomes in human serum.
• To determine if immunoglobulin depletion affects the efficiency of complement activation by anionic phospholipids in liposomes.

Main Methods:

• Liposomes containing various negatively charged phospholipids were prepared.
• Complement activation was assessed using hemolytic assays, C1q ELISA, and crossed immunoelectrophoresis.
• Normal human serum (NHS) and immunoglobulin-depleted serum (DDS) were used to compare complement activation.

Main Results:

• Higher concentrations of phospholipids were required to activate complement in immunoglobulin-depleted serum compared to NHS.
• Complement activation via the classical pathway was confirmed to be C1q-dependent and reduced in the absence of immunoglobulins.
• iC3b, a complement opsonin, was detected on liposomes incubated with both NHS and DDS, indicating complement protein deposition.

Conclusions:

• Immunoglobulins play a crucial role in enhancing liposome-induced complement activation in human serum.
• Anionic phospholipids in liposomes can activate complement even in the absence of immunoglobulins, but less efficiently.
• Liposomes with anionic phospholipids become opsonized by complement proteins, a process modulated by immunoglobulin presence.