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Updated: Mar 13, 2026

A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
Published on: December 9, 2021
GEF-H1 is necessary for neutrophil shear stress-induced migration during inflammation
Noah Fine1, Ioannis D Dimitriou2, Jacob Rullo3
1Princess Margaret Cancer Center, Toronto, Ontario M5G 1L7, Canada Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5S 1L7, Canada Matrix Dynamics Group, University of Toronto, Toronto, Ontario M5S 3E2, Canada.
Abstract:
Leukocyte crawling and transendothelial migration (TEM) are potentiated by shear stress caused by blood flow. The mechanism that couples shear stress to migration has not been fully elucidated. We found that mice lacking GEF-H1 (GEF-H1-/-), a RhoA-specific guanine nucleotide exchange factor (GEF), displayed limited migration and recruitment of neutrophils into inflamed tissues. GEF-H1-/- leukocytes were deficient in in vivo crawling and TEM in the postcapillary venules. We demonstrated that although GEF-H1 deficiency had little impact on the migratory properties of neutrophils under static conditions, shear stress triggered GEF-H1-dependent spreading and crawling of neutrophils and relocalization of GEF-H1 to flotillin-2-rich uropods. Our results identify GEF-H1 as a component of the shear stress response machinery in neutrophils required for a fully competent immune response to bacterial infection.
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