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Related Experiment Videos

Distinct restriction of complement- and cell-mediated lysis.

N Hollander1, M L Shin, W F Rosse

  • 1Rorer Biotechnology Inc., King of Prussia, PA 19406.

Journal of Immunology (Baltimore, Md. : 1950)
|June 1, 1989
PubMed
Summary

Phosphatidylinositol glycan (PIG)-anchored proteins protect against complement-mediated lysis but not cell-mediated killing. This suggests distinct protective mechanisms against different immune attack pathways, impacting cellular defense strategies.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Complement- and cell-mediated killing pathways share effector proteins (C8/C9 and perforin).
  • Similar protective proteins might exist against both complement and cell-mediated attacks.
  • Two known protective proteins against complement lysis are anchored by phosphatidylinositol glycan (PIG) tails.

Purpose of the Study:

  • To investigate if PIG-anchored proteins also protect against lymphocyte-mediated killing.
  • To determine the role of PIG-tailed proteins in cellular defense against immune attack.

Main Methods:

  • Utilized nucleated cell lines with mutations in PIG anchor biosynthesis.
  • Assessed sensitivity to homologous complement-mediated lysis.
  • Evaluated resistance to three distinct types of cell-mediated killing and purified perforin lysis.

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  • Examined erythrocyte (E) sensitivity to antibody-dependent cell-mediated cytotoxicity in patients with PIG biosynthesis defects.

    • Main Results:

    • PIG-tailed membrane proteins restrict homologous complement-mediated lysis.
    • These proteins do not restrict lysis mediated by three different cell types or by purified perforin.
    • Erythrocytes from patients with acquired PIG tail biosynthesis defects showed no difference in sensitivity to antibody-dependent cell-mediated cytotoxicity compared to normal erythrocytes.
    • These patient erythrocytes were more sensitive to human C8 and C9.

    Conclusions:

    • PIG-tailed membrane proteins specifically protect against complement-mediated lysis, not cell-mediated killing.
    • Cellular defense against complement and cell-mediated attacks involves distinct protective mechanisms.
    • The findings highlight the specific role of PIG-anchored proteins in resisting complement attack.