Neutrophils sense flow-generated stress and direct their migration using anchorage through αVβ3-integrin

Christopher Buckley, George Rainger, DL Simmons, Gerard Nash

Research output: Contribution to journalArticlepeer-review

Abstract

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 αVβ3-integrin with monoclonal antibodies or turning the flow off randomized the direction of migration without affecting migration velocity. Purified, immobilized αVβ3-integrin ligands, CD31 and fibronectin, could both support flow-directed neutrophil migration in a concentration-dependent manner. Migration could be randomized by neutralizing αVβ3-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.
Original languageEnglish
Pages (from-to)858-864
Number of pages7
JournalAmerican Journal of Physiology
Volume276
Issue number3
Publication statusPublished - 1 Mar 1999

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