M-ficolin and leukosialin (CD43): new partners in neutrophil adhesion

Andrea N Moreno-Amaral1, Evelyne Gout, Claudia Danella-Polli

  • 1Batiment Lavoisier, Hôpital Necker, 149 rue de Sevres, Paris, France.

Insights

M-ficolin binds to CD43 on neutrophils, modulating their adhesion and aggregation. This interaction, distinct from pathogen recognition, highlights M-ficolin's role in early inflammation and neutrophil recruitment.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • M-ficolin is a lectin known for pathogen recognition.
  • CD43 is a major sialoprotein on human neutrophils with anti-adhesive properties.

Purpose of the Study:

  • To investigate the interaction between M-ficolin and CD43 on human neutrophils.
  • To determine the functional consequences of this interaction on neutrophil behavior and complement activation.

Main Methods:

  • Recombinant M-ficolin (rM-ficolin) binding assays to neutrophils and Western blots.
  • Analysis of M-ficolin secretion by fMLP-activated neutrophils.
  • Immunofluorescence microscopy to assess colocalization of M-ficolin and CD43.
  • Functional assays measuring neutrophil polarization, adhesion, and aggregation.
  • Assessment of M-ficolin's effect on the lectin complement pathway.

Main Results:

  • rM-ficolin binds specifically to CD43 on neutrophils, inhibiting anti-CD43 mAb binding.
  • Endogenous M-ficolin secreted by activated neutrophils also binds CD43.
  • M-ficolin and CD43 colocalize on activated neutrophils.
  • rM-ficolin binding induces neutrophil polarization, adhesion, and aggregation.
  • A M-ficolin mutant unable to bind sialic acid did not interact with neutrophils.
  • rM-ficolin activated the lectin complement pathway on neutrophils.

Conclusions:

  • M-ficolin interacts with CD43 on neutrophils, mediating novel adhesive functions.
  • This interaction is independent of M-ficolin's known pathogen recognition role.
  • M-ficolin binding to CD43 contributes to neutrophil adhesion and aggregation in early inflammation.
  • M-ficolin may explain the dual adhesive/anti-adhesive roles of CD43 in neutrophil recruitment.
  • M-ficolin activates the complement system on neutrophils.

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