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Related Experiment Videos

Species- and cell type-specific interactions between CD47 and human SIRPalpha.

Shyamsundar Subramanian1, Ranganath Parthasarathy, Shamik Sen

  • 1School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.

Blood
|November 18, 2005
PubMed
Summary

The CD47-SIRPalpha interaction, a "self" signal, shows limited cross-species reactivity and cell-type specificity. This binding is not responsible for red blood cell clearance in humans under physiological conditions.

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Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • The CD47 protein on red blood cells (RBCs) is known to signal
  • self
  • to phagocytes via SIRPalpha, particularly in mice.
  • The cross-species and cell-type specificity of this interaction, crucial for understanding immune responses and cell adhesion, remains unclear.

Purpose of the Study:

  • To investigate the species-specific and cell-type-specific binding of human SIRPalpha1 to CD47.
  • To determine the role of CD47-SIRPalpha interactions in red blood cell adhesion and clearance.
  • To explore potential avidity enhancement mechanisms in SIRPalpha-CD47 binding.

Main Methods:

  • Utilized human SIRPalpha1 as a probe to detect CD47 binding on various species' RBCs.

Related Experiment Videos

  • Employed antibody inhibition assays and atomic force microscopy to assess CD47-mediated adhesion.
  • Investigated binding to CD47 on bone marrow-derived mesenchymal stem cells.

    • Main Results:

    • Antibody-inhibitable CD47 binding to human SIRPalpha1 was observed only with human and pig RBCs.
    • CD47-mediated adhesion of human and pig RBCs to SIRPalpha1 surfaces demonstrated force resistance but required high SIRPalpha1 densities.
    • Low CD47 copy numbers on phagocytes and lack of significant binding to mesenchymal stem cells suggest limited physiological relevance for RBC clearance.

    Conclusions:

    • SIRPalpha-CD47 interactions exhibit significant cell type specificity and limited cross-species reactivity.
    • The study refutes the role of this specific interaction in physiological red blood cell clearance in humans.
    • Evidence of clustering suggests potential avidity enhancement mechanisms warranting further investigation.