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Related Experiment Video

Updated: Apr 30, 2026

A Flow Adhesion Assay to Study Leucocyte Recruitment to Human Hepatic Sinusoidal Endothelium Under Conditions of Shear Stress
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alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow

C Berlin1, R F Bargatze, J J Campbell

  • 1Department of Pathology, Stanford University, California 94305.

Cell
|February 10, 1995
PubMed
Summary

Alpha 4 (CD49d) integrins initiate lymphocyte adhesion under shear flow, independent of selectins. These integrins, unlike beta 2 integrins, are crucial for initial leukocyte interactions and attachment.

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Assay of Adhesion Under Shear Stress for the Study of T Lymphocyte-Adhesion Molecule Interactions
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Area of Science:

  • Immunology
  • Cell Biology
  • Biophysics

Background:

  • Leukocyte-endothelial cell interactions are critical for immune responses.
  • Selectins initiate leukocyte rolling under physiological shear, preceding integrin-mediated arrest.
  • Beta 2 (CD18) integrins require selectin engagement for neutrophil adhesion.

Purpose of the Study:

  • To investigate the role of alpha 4 (CD49d) integrins in initiating leukocyte adhesion under shear flow.
  • To determine if alpha 4 integrins can mediate adhesion independently of selectins.
  • To elucidate the mechanism of alpha 4 integrin-mediated adhesion, including ligand interactions and topographic presentation.

Main Methods:

  • In vitro shear flow assays to assess lymphocyte tethering and rolling.
  • In situ studies of lymphocyte attachment to lamina propria venules.
  • Scanning electron microscopy to visualize integrin distribution on lymphoid cells.

Main Results:

  • Alpha 4 (CD49d) integrins initiate lymphocyte tethering under shear, without selectin involvement.
  • Alpha 4 integrin ligands (MAdCAM-1, VCAM-1) support rolling and activation-dependent arrest.
  • Alpha 4 beta 7 mediates L-selectin-independent lymphocyte adhesion in vivo.
  • Alpha 4 beta 7 is concentrated on microvilli, facilitating initial contact, while beta 2 integrins are excluded.

Conclusions:

  • Alpha 4 integrins, but not beta 2 integrins, can initiate leukocyte adhesion under flow conditions.
  • The topographic presentation of alpha 4 integrins on microvilli contributes to their role in initiating adhesion.
  • These findings reveal a distinct mechanism for lymphocyte adhesion initiation mediated by alpha 4 integrins.