The metalloprotease ADAM8 is associated with and regulates the function of the adhesion receptor PSGL-1 through ERM

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Maria Domínguez-Luis1, Amalia Lamana, Jesús Vazquez

  • 1Servicio de Reumatología, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain.

European Journal of Immunology
|January 10, 2012
PubMed

Insights

The metalloprotease ADAM8 cleaves P-selectin glycoprotein ligand-1 (PSGL-1), reducing leukocyte rolling on activated endothelial cells. ADAM8 regulates PSGL-1 expression and function, impacting leukocyte adhesion.

Area of Science:

  • Cellular and Molecular Biology
  • Immunology
  • Biochemistry

Background:

  • P-selectin glycoprotein ligand-1 (PSGL-1) mediates initial leukocyte contact with activated endothelium.
  • The adhesive function of PSGL-1 is regulated by proteolytic processing.
  • Understanding PSGL-1 regulation is crucial for immune cell trafficking.

Purpose of the Study:

  • To investigate the role of the metalloprotease ADAM8 in the regulation of PSGL-1.
  • To determine if ADAM8 is associated with PSGL-1 and affects its proteolytic processing.
  • To assess the functional impact of ADAM8 on leukocyte adhesion.

Main Methods:

  • Biochemical assays to determine the association between ADAM8 and PSGL-1 via ezrin–radixin–moesin proteins.
  • ADAM8 knockdown experiments to evaluate changes in PSGL-1 expression.
  • Functional assays measuring leukocyte rolling on P-selectin and activated endothelial cells.

Main Results:

  • ADAM8 was found to be associated with PSGL-1 through actin-binding proteins.
  • ADAM8 directly cleaves PSGL-1, reducing its expression.
  • Knockdown of ADAM8 increased PSGL-1 expression and reduced leukocyte rolling on P-selectin and activated endothelial cells.

Conclusions:

  • ADAM8 modulates the expression and adhesive function of PSGL-1.
  • ADAM8 plays a significant role in regulating leukocyte-endothelial cell interactions.
  • Targeting ADAM8 could offer a strategy to control leukocyte adhesion in inflammatory conditions.

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