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A comparative study of complement activation.

D A Higgins, D J Langley

    Veterinary Immunology and Immunopathology
    |May 1, 1985
    PubMed
    Summary
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    This study investigated complement activation in various animal sera using sheep erythrocytes. Guinea-pig complement was highly active, while human complement showed selectivity, and alternative pathway activation varied significantly between species.

    Area of Science:

    • Immunology
    • Complement System
    • Comparative Immunology

    Background:

    • The complement system is crucial for innate immunity.
    • Understanding cross-species complement activation is vital for immunological research.
    • Variations in complement pathways across species remain incompletely understood.

    Purpose of the Study:

    • To investigate the cross-activation of total hemolytic complement (THCA) and total alternative pathway activity (TAPA) using antisera raised in various animal species against sheep erythrocytes.
    • To characterize the kinetic differences in complement activation and lysis.
    • To identify species-specific patterns in complement activation.

    Main Methods:

    • Generation of antisera in cattle, rabbits, mice, hamsters, guinea-pigs, ferrets, badgers, hedgehogs, and fowls against sheep erythrocytes.

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  • Assays for total hemolytic complement (THCA) and total alternative pathway activity (TAPA) across various species combinations.
  • Kinetic assays to analyze the kinetics of erythrocyte lysis.
  • Agarose gel electrophoresis to assess complement activation.

    • Main Results:

    • Ox, rabbit, and fowl sera exhibited low THCA, while guinea-pig complement was universally active. Human complement demonstrated marked selectivity.
    • Ferret, badger, and hedgehog sera showed high activation titres, likely via the alternative pathway.
    • An inverse relationship was observed between serum complement activity and erythrocyte activating ability within the same species.
    • Rabbit and rodent erythrocytes were efficient alternative pathway activators, whereas badger, ferret, and fowl sera showed the broadest response.
    • Kinetic studies indicated that initiation and completion of lysis could be separate events in complement activation.

    Conclusions:

    • Complement activation pathways exhibit significant species-specific variations.
    • The alternative pathway plays a prominent role in complement activation by certain xenogeneic erythrocytes.
    • Distinct kinetic profiles suggest sequential and potentially separable steps in complement-mediated lysis.