Hyun Y-M, Sumagin R, Sarangi PP et al.Uropod elongation is a common final step in leukocyte extravasation through inflamed vessels. J Exp Med 209:1349-1362

Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, USA.
Journal of Experimental Medicine (Impact Factor: 12.52). 06/2012; 209(7):1349-62. DOI: 10.1084/jem.20111426
Source: PubMed


The efficient trafficking of immune cells into peripheral nonlymphoid tissues is key to enact their protective functions. Despite considerable advances in our understanding of cell migration in secondary lymphoid organs, real-time leukocyte recruitment into inflamed tissues is not well characterized. The conventional multistep paradigm of leukocyte extravasation depends on CD18 integrin-mediated events such as rapid arrest and crawling on the surface of the endothelium and transmigration through the endothelial layer. Using enhanced three-dimensional detection of fluorescent CD18 fusion proteins in a newly developed knockin mouse, we report that extravasating leukocytes (neutrophils, monocytes, and T cells) show delayed uropod detachment and become extremely elongated before complete transmigration across the endothelium. Additionally, these cells deposit CD18(+) microparticles at the subendothelial layer before retracting the stretched uropod. Experiments with knockout mice and blocking antibodies reveal that the uropod elongation and microparticle formation are the result of LFA-1-mediated adhesion and VLA-3-mediated cell migration through the vascular basement membrane. These findings suggest that uropod elongation is a final step in the leukocyte extravasation cascade, which may be important for precise regulation of leukocyte recruitment into inflamed tissues.

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    • "To understand the mechanism that might underlie the effect of PKCθ on migration to lymph nodes, we determined the effect of PKCθ on uropod formation. Migrating T cell uropods have recently been shown to be crucial for migration into lymph nodes via transendothelial migration, likely through a role in force generation [6], [30]. Uropod formation is regulated in part by specific cytoskeletal protein localization to the uropod which can control both uropod formation and migration [6]. "
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    • "These data strongly implicate the role of LFA-1 activity regulation also in in vivo homing, although the contribution of slight changes in the LFA-1 expression levels was not formally excluded. In fact, LFA-1-dependent uropod elongation has very recently been proposed to be a final common step during transendothelial migration (Hyun et al., 2012). Therefore, a release mechanism is needed before the cell can migrate further into the tissue, and we postulate that SHARPIN, which is enriched in the uropod of extravasating leukocytes, facilitates homing, and enhances cell movement after transendothelial migration, could play an important role in this process. "
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