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Related Experiment Videos

Cholesterol-dependent human complement activation resulting in damage to liposomal model membranes

C R Alving, R L Richards, A A Guirguis

    Journal of Immunology (Baltimore, Md. : 1950)
    |January 1, 1977
    PubMed
    Summary

    High cholesterol in liposomes triggers human complement activation, causing membrane damage. This immune response is influenced by lipid composition and mediated by a heat-labile serum factor, suggesting classical complement pathway involvement.

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    Area of Science:

    • Immunology
    • Biochemistry
    • Lipid Bilayer Research

    Background:

    • Liposomes are frequently used in drug delivery and research.
    • The complement system is a crucial part of innate immunity.
    • Understanding liposome-host interactions is vital for biomedical applications.

    Purpose of the Study:

    • To investigate the spontaneous activation of human complement by liposomes.
    • To determine the role of cholesterol concentration and lipid composition in complement activation.
    • To identify the serum factors involved in this complement-mediated damage.

    Main Methods:

    • Liposomes with varying cholesterol concentrations and lipid compositions were prepared.
    • Human and guinea pig sera were incubated with liposomes.

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  • Complement activation was assessed by measuring liposomal glucose release.
  • Heat lability and inhibitory factors were investigated.

    • Main Results:

    • High cholesterol (71 mol%) in liposomes spontaneously activated human complement, causing membrane damage and glucose release.
    • Complement activation did not occur at low cholesterol (43 mol%) or with sphingomyelin-based liposomes.
    • A heat-labile serum factor, not present in guinea pig serum, mediated this activation, suggesting the classical complement pathway.
    • Liposomal lipid composition, including galactosyl ceramide and lecithin acyl chain length, influenced complement activity.

    Conclusions:

    • High membrane cholesterol concentrations in liposomes can spontaneously activate the human complement system.
    • This activation is mediated by an uncharacterized, partially heat-labile serum factor.
    • The lipid composition of the liposomal membrane significantly influences complement activation.
    • These findings have implications for the design of liposomal drug delivery systems.