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Related Experiment Videos

Interaction between complement proteins C5b-7 and erythrocyte membrane sialic acid

P Marshall1, A Hasegawa, E A Davidson

  • 1Dermatology Service, Veterans Affairs Medical Center, New York 10016, USA.

The Journal of Experimental Medicine
|October 1, 1996
PubMed
Summary

Sialic acid on red blood cells initially hinders complement C5b6 binding but surprisingly enhances membrane attack once initiated. This reveals a dual role for sialic acid in the complement cascade.

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Bioscience, biotechnology, and biochemistry·1995

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • The complement system's membrane attack complex (MAC) formation is crucial for cell lysis.
  • Initial steps involve C5b6, C7 interaction with cell membranes to form C5b-7.
  • Sialic acid's role in this early membrane attack phase is not fully understood.

Purpose of the Study:

  • To investigate the specific role of sialic acid residues in C5b-7 assembly on erythrocyte membranes.
  • To elucidate the binding interactions of complement proteins C5b6, C5, and C6 with erythrocyte surface molecules.

Main Methods:

  • Studied C5b6 binding to glycophorin on erythrocyte membranes.
  • Investigated the effect of desialylation and sialic acid masking (using mAb F(ab) fragments) on C5b6 binding.

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  • Assessed inhibition of C5b-7 deposition by gangliosides and asialogangliosides.
  • Main Results:

    • C5b6 specifically binds to glycophorin; C5 or C6 do not.
    • Desialylation of glycophorin abolishes C5b6 binding.
    • Masking or removing sialic acid from glycophorin inhibits complement lysis.
    • Gangliosides inhibit C5b-7 deposition, but asialogangliosides do not.

    Conclusions:

    • C5b6 initially binds to erythrocyte membranes via ionic interactions with sialylated molecules.
    • A model is proposed where C7 binding to C5b6 disrupts ionic interactions, exposing hydrophobic domains.
    • Sialic acid plays a paradoxical role: inhibiting initial C5b6 generation but enhancing lysis once the membrane attack pathway is initiated.