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Related Experiment Videos

The leukocyte integrin alpha D beta 2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1.

M Van der Vieren1, D T Crowe, D Hoekstra

  • 1ICOS Corp., Bothell, WA 98021, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|August 10, 1999
PubMed
Summary

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Alpha D beta 2 integrin binds vascular cell adhesion molecule 1 (VCAM-1), mediating leukocyte adhesion. This interaction is crucial for leukocyte trafficking, particularly for cells expressing alpha D beta 2.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Leukocyte trafficking is essential for immune responses and relies on integrin-ligand interactions.
  • Beta 2 integrins, such as LFA-1 and Mac-1, bind ICAM-1, facilitating leukocyte adhesion.
  • Alpha D beta 2 is a recently identified beta 2 integrin that binds ICAM-3.

Purpose of the Study:

  • To investigate the binding properties of alpha D beta 2 integrin to VCAM-1.
  • To determine the functional significance of alpha D beta 2 binding to VCAM-1 in leukocyte adhesion.

Main Methods:

  • Expression of alpha D beta 2 in lymphoid cells lacking alpha 4 integrins.
  • Binding assays using soluble alpha D beta 2 and VCAM-1 mutants.
  • Flow adhesion assays under dynamic flow conditions.

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Main Results:

  • Alpha D beta 2 efficiently binds VCAM-1, independent of alpha 4 integrins.
  • The I domain of alpha D mediates VCAM-1 binding, overlapping with alpha 4 integrin binding sites.
  • Alpha D beta 2 supports lymphoid cell adhesion to VCAM-1 under flow, comparable to alpha 4 beta 1.

Conclusions:

  • VCAM-1 serves as a ligand for the I domain of alpha D beta 2.
  • Alpha D beta 2-VCAM-1 interaction contributes to the trafficking of specific leukocyte subsets.
  • This finding expands the known ligands for beta 2 integrins and their roles in immune cell migration.