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Am J Physiol Heart Circ Physiol 276: H858-H864, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 3, H858-H864, March 1999

Neutrophils sense flow-generated stress and direct their migration through alpha Vbeta 3-integrin

G. E. Rainger1, C. D. Buckley2, D. L. Simmons3, and G. B. Nash1

Departments of 1 Physiology and 2 Rheumatology, The Medical School, The University of Birmingham, Edgbaston, Birmingham B15 2TT; and 3 Cell Adhesion Laboratory, University of Oxford, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom

During inflammation neutrophils are recruited from the blood onto the surface of microvascular endothelial cells. In this milieu the presence of soluble chemotactic gradients is disallowed by blood flow. However, directional cues are still required for neutrophils to migrate to the junctions of endothelial cells where extravasation occurs. Shear forces generated by flowing blood provide a potential alternative guide. In our flow-based adhesion assay neutrophils preferentially migrated in the direction of flow when activated after attachment to platelet monolayers. Neutralizing alpha Vbeta 3-integrin with monoclonal antibodies or turning the flow off randomized the direction of migration without affecting migration velocity. Purified, immobilized alpha Vbeta 3-integrin ligands, CD31 and fibronectin, could both support flow-directed neutrophil migration in a concentration-dependent manner. Migration could be randomized by neutralizing alpha Vbeta 3-integrin interactions with the substrate using antibodies or Arg-Gly-Asp-containing peptide. These results exemplify mechanical signal transduction through integrin-ligand interactions and reveal a guidance system that was hitherto unknown in neutrophils. In more general terms, it demonstrates that cells can use integrin molecules to "sample" their physical microenvironment through adhesion and use this information to modulate their behavior.

integrin signaling; adhesion molecule cross talk; regulated migration


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