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Alternative complement pathway activation by C4b deposited during classical pathway activation.

M Matsushita, H Okada

    Journal of Immunology (Baltimore, Md. : 1950)
    |April 15, 1986
    PubMed
    Summary
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    Sheep erythrocytes sensitized with antibodies were used to study complement pathway activation. The results indicate that C4b molecules on the cell membrane can activate the alternative complement pathway.

    Area of Science:

    • Immunology
    • Complement System
    • Cellular Immunology

    Background:

    • The complement system is a crucial part of innate immunity.
    • Understanding complement activation pathways is vital for immunology research.
    • The role of C4b in complement activation requires further elucidation.

    Purpose of the Study:

    • To investigate the role of C4b molecules in complement activation.
    • To determine if C4b can mediate hemolysis via the alternative complement pathway.

    Main Methods:

    • Sheep erythrocytes were sensitized with antibodies and complement components (C1, C4) to form EAC1,4b.
    • EDTA treatment generated EAC4b intermediates.
    • Hemolytic assays were performed using human or guinea pig serum under specific buffer conditions (Mg-EGTA-GVB).

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    Main Results:

    • EAC4b intermediates were lysed by serum, independent of the classical pathway's C3 convertase.
    • Hemolysis was mediated by the alternative complement pathway (ACP).
    • Pretreatment with anti-C4 or C4-binding protein suppressed ACP-mediated hemolysis.
    • EAC4b were more sensitive to hemolysis than EAC1q.

    Conclusions:

    • C4b molecules on the cell membrane are capable of activating the alternative complement pathway.
    • This finding provides new insights into complement system regulation and function.