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Related Experiment Videos

Membrane vesiculation protects erythrocytes from destruction by complement.

K Iida1, M B Whitlow, V Nussenzweig

  • 1Department of Pathology, New York University Medical Center, NY 10016.

Journal of Immunology (Baltimore, Md. : 1950)
|October 15, 1991
PubMed
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Red blood cells can eliminate the membrane attack complex (MAC) via microvesicles, preventing cell lysis. This calcium-dependent process, observed in human and guinea pig cells but not SRBC, offers a novel defense mechanism against complement-mediated damage.

Area of Science:

  • Immunology
  • Cell Biology
  • Complement System

Background:

  • Nucleated cells resist complement (C) attack via exocytosis/endocytosis of the membrane attack complex (MAC).
  • The one-hit theory posits that a single MAC channel on erythrocytes (E) leads to lysis.
  • Existing complement regulatory proteins (CD59, C8bp/HRF) prevent MAC assembly.

Purpose of the Study:

  • To investigate if erythrocytes possess mechanisms to eliminate MAC and escape complement-mediated lysis.
  • To determine the role of calcium (Ca2+) in MAC elimination and erythrocyte protection.

Main Methods:

  • Incubation of human and guinea pig erythrocytes (E) and SRBC with C5b-9 (MAC).
  • Monitoring of vesiculation and cell lysis in response to MAC attack.
  • Quantification of Ca2+ influx and its effect on vesiculation and lysis.

Related Experiment Videos

  • Analysis of MAC component (C9) enrichment in released vesicles.
  • Main Results:

    • Human and guinea pig E, but not SRBC, eliminate MAC via microvesicle release, preventing lysis.
    • Vesiculation occurs without a lag phase and is Ca2+ influx-dependent.
    • Increased Ca2+ concentration correlates with increased vesiculation and decreased lysis.
    • Released vesicles from guinea pig E are significantly enriched in C9.

    Conclusions:

    • Erythrocytes possess a Ca2+-dependent mechanism to eliminate MAC through vesiculation, providing protection from complement-mediated lysis.
    • This MAC elimination pathway complements known regulatory proteins like CD59 and C8bp/HRF.
    • Selective MAC elimination represents a novel host defense strategy against complement attack.