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Related Experiment Videos

Decay-accelerating factor functions as a signal transducing molecule for human monocytes.

K Shibuya1, T Abe, T Fujita

  • 1Institute of Clinical Medicine, University of Tsukuba, Japan.

Journal of Immunology (Baltimore, Md. : 1950)
|September 1, 1992
PubMed
Summary

Monoclonal antibody 1C6 activates human monocytes by blocking decay-accelerating factor (DAF), enhancing glucose consumption and phagocytosis. This DAF-mediated monocyte activation involves signaling pathways, including inositol trisphosphate generation.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Decay-accelerating factor (DAF) is a membrane protein protecting cells from complement-mediated damage.
  • Monoclonal antibodies (mAbs) can modulate cellular functions by targeting specific membrane proteins.

Purpose of the Study:

  • To investigate whether human monocytes are activated through decay-accelerating factor (DAF) molecules.
  • To identify the signaling pathways involved in DAF-mediated monocyte activation.

Main Methods:

  • Incubation of human monocytes with anti-DAF mAbs (1C6 and 5B2) and their fragments.
  • Measurement of glucose consumption and phagocytosis of latex beads.
  • Analysis of monokine production (TNF-alpha, IL-1 alpha, IL-1 beta).
  • Treatment with phosphatidylinositol-specific phospholipase C (PI-PLC) and measurement of inositol trisphosphate generation.

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Main Results:

  • Monocyte incubation with 1C6 mAb resulted in significant glucose consumption and enhanced phagocytosis, indicating activation.
  • 1C6-mediated monocyte activation was dependent on the F(ab')2 fragment but not the Fab fragment.
  • PI-PLC treatment reduced 1C6-induced glucose consumption and phagocytosis.
  • 1C6 stimulated the generation of inositol trisphosphate in monocytes.

Conclusions:

  • The signal transmitted via decay-accelerating factor (DAF) can activate human monocytes.
  • DAF-mediated monocyte activation involves phosphatidylinositol-specific phospholipase C-sensitive signaling pathways and inositol trisphosphate generation.